Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Receptor-Like Protein Tyrosine Phosphatases, Class 8: A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.RNA, Small Cytoplasmic: Small RNAs found in the cytoplasm usually complexed with proteins in scRNPs (RIBONUCLEOPROTEINS, SMALL CYTOPLASMIC).Diabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Orchitis: Inflammation of a TESTIS. It has many features of EPIDIDYMITIS, such as swollen SCROTUM; PAIN; PYURIA; and FEVER. It is usually related to infections in the URINARY TRACT, which likely spread to the EPIDIDYMIS and then the TESTIS through either the VAS DEFERENS or the lymphatics of the SPERMATIC CORD.Ribonucleoproteins: Complexes of RNA-binding proteins with ribonucleic acids (RNA).CapZ Actin Capping Protein: An actin capping protein that binds to the barbed-ends of ACTIN filaments. It is a heterodimer consisting of an alpha and a beta subunit. It regulates actin assembly by stabilizing actin oligomers for elongation. In SKELETAL MUSCLE, CapZ is localized to the Z-disk.Liver Cirrhosis, Biliary: FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.Epitopes: Sites on an antigen that interact with specific antibodies.snRNP Core Proteins: The protein components that constitute the common core of small nuclear ribonucleoprotein particles. These proteins are commonly referred as Sm nuclear antigens due to their antigenic nature.CitrullineAlopecia Areata: Loss of scalp and body hair involving microscopically inflammatory patchy areas.Serology: The study of serum, especially of antigen-antibody reactions in vitro.Protein Tyrosine Phosphatase, Non-Receptor Type 1: A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.Mice, Inbred NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Molecular Mimicry: The structure of one molecule that imitates or simulates the structure of a different molecule.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.Proinsulin: A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Protein Array Analysis: Ligand-binding assays that measure protein-protein, protein-small molecule, or protein-nucleic acid interactions using a very large set of capturing molecules, i.e., those attached separately on a solid support, to measure the presence or interaction of target molecules in the sample.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.Uveitis: Inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (sclera and cornea, and the retina). (Dorland, 27th ed)Sjogren's Syndrome: Chronic inflammatory and autoimmune disease in which the salivary and lacrimal glands undergo progressive destruction by lymphocytes and plasma cells resulting in decreased production of saliva and tears. The primary form, often called sicca syndrome, involves both KERATOCONJUNCTIVITIS SICCA and XEROSTOMIA. The secondary form includes, in addition, the presence of a connective tissue disease, usually rheumatoid arthritis.Self Tolerance: The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Myositis: Inflammation of a muscle or muscle tissue.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.Polyendocrinopathies, Autoimmune: Autoimmune diseases affecting multiple endocrine organs. Type I is characterized by childhood onset and chronic mucocutaneous candidiasis (CANDIDIASIS, CHRONIC MUCOCUTANEOUS), while type II exhibits any combination of adrenal insufficiency (ADDISON'S DISEASE), lymphocytic thyroiditis (THYROIDITIS, AUTOIMMUNE;), HYPOPARATHYROIDISM; and gonadal failure. In both types organ-specific ANTIBODIES against a variety of ENDOCRINE GLANDS have been detected. The type II syndrome differs from type I in that it is associated with HLA-A1 and B8 haplotypes, onset is usually in adulthood, and candidiasis is not present.Myelin Basic Protein: An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes.Dihydrolipoyllysine-Residue Acetyltransferase: An enzyme that catalyzes the acetyltransferase reaction using ACETYL CoA as an acetyl donor and dihydrolipoamide as acceptor to produce COENZYME A (CoA) and S-acetyldihydrolipoamide. It forms the (E2) subunit of the PYRUVATE DEHYDROGENASE COMPLEX.Hepatitis, Autoimmune: A chronic self-perpetuating hepatocellular INFLAMMATION of unknown cause, usually with HYPERGAMMAGLOBULINEMIA and serum AUTOANTIBODIES.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Scleroderma, Systemic: A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.Antigen Presentation: The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)Insulin Antibodies: Antibodies specific to INSULIN.Mice, Inbred NZBHybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Vasectomy: Surgical removal of the ductus deferens, or a portion of it. It is done in association with prostatectomy, or to induce infertility. (Dorland, 28th ed)Electrophoresis, Gel, Two-Dimensional: Electrophoresis in which a second perpendicular electrophoretic transport is performed on the separate components resulting from the first electrophoresis. This technique is usually performed on polyacrylamide gels.Centromere Protein B: A DNA-binding protein that interacts with a 17-base pair sequence known as the CENP-B box motif. The protein is localized constitutively to the CENTROMERE and plays an important role in its maintenance.Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached.Paraneoplastic Syndromes: In patients with neoplastic diseases a wide variety of clinical pictures which are indirect and usually remote effects produced by tumor cell metabolites or other products.Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.Thyroiditis, Autoimmune: Inflammatory disease of the THYROID GLAND due to autoimmune responses leading to lymphocytic infiltration of the gland. It is characterized by the presence of circulating thyroid antigen-specific T-CELLS and thyroid AUTOANTIBODIES. The clinical signs can range from HYPOTHYROIDISM to THYROTOXICOSIS depending on the type of autoimmune thyroiditis.Ribonucleoproteins, Small Nuclear: Highly conserved nuclear RNA-protein complexes that function in RNA processing in the nucleus, including pre-mRNA splicing and pre-mRNA 3'-end processing in the nucleoplasm, and pre-rRNA processing in the nucleolus (see RIBONUCLEOPROTEINS, SMALL NUCLEOLAR).Phosphopyruvate Hydratase: A hydro-lyase that catalyzes the dehydration of 2-phosphoglycerate to form PHOSPHOENOLPYRUVATE. Several different isoforms of this enzyme exist, each with its own tissue specificity.Ribonucleoprotein, U1 Small Nuclear: A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U1 snRNP along with other small nuclear ribonucleoproteins (U2, U4-U6, and U5) assemble into SPLICEOSOMES that remove introns from pre-mRNA by splicing. The U1 snRNA forms base pairs with conserved sequence motifs at the 5'-splice site and recognizes both the 5'- and 3'-splice sites and may have a fundamental role in aligning the two sites for the splicing reaction.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Epitopes, T-Lymphocyte: Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.Anemia, Hemolytic, Autoimmune: Acquired hemolytic anemia due to the presence of AUTOANTIBODIES which agglutinate or lyse the patient's own RED BLOOD CELLS.Mice, Inbred MRL lpr: A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.Gene Library: A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.Receptors, Thyrotropin: Cell surface proteins that bind pituitary THYROTROPIN (also named thyroid stimulating hormone or TSH) and trigger intracellular changes of the target cells. TSH receptors are present in the nervous system and on target cells in the thyroid gland. Autoantibodies to TSH receptors are implicated in thyroid diseases such as GRAVES DISEASE and Hashimoto disease (THYROIDITIS, AUTOIMMUNE).Mice, Inbred C57BLCD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Rats, Inbred LewEpitopes, B-Lymphocyte: Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.HLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.Iodide Peroxidase: A hemeprotein that catalyzes the oxidation of the iodide radical to iodine with the subsequent iodination of many organic compounds, particularly proteins. EC 1.11.1.8.Mice, Inbred BALB CAntigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Prediabetic State: The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).Myeloblastin: A polymorphonuclear leukocyte-derived serine protease that degrades proteins such as ELASTIN; FIBRONECTIN; LAMININ; VITRONECTIN; and COLLAGEN. It is named for its ability to control myeloid cell growth and differentiation.Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Fluorescent Antibody Technique, Indirect: A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Polymyositis: Diseases characterized by inflammation involving multiple muscles. This may occur as an acute or chronic condition associated with medication toxicity (DRUG TOXICITY); CONNECTIVE TISSUE DISEASES; infections; malignant NEOPLASMS; and other disorders. The term polymyositis is frequently used to refer to a specific clinical entity characterized by subacute or slowly progressing symmetrical weakness primarily affecting the proximal limb and trunk muscles. The illness may occur at any age, but is most frequent in the fourth to sixth decade of life. Weakness of pharyngeal and laryngeal muscles, interstitial lung disease, and inflammation of the myocardium may also occur. Muscle biopsy reveals widespread destruction of segments of muscle fibers and an inflammatory cellular response. (Adams et al., Principles of Neurology, 6th ed, pp1404-9)Lupus Vulgaris: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the NASAL MUCOSA; BUCCAL MUCOSA; and conjunctival mucosa.Hippocalcin: A neuronal calcium-sensor protein that was initially found in the NEURONS of the HIPPOCAMPUS. It interacts with NEURONAL APOPTOSIS-INHIBITORY PROTEIN.Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Proteomics: The systematic study of the complete complement of proteins (PROTEOME) of organisms.Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Lupus Nephritis: Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Immunomodulation: Alteration of the immune system or of an immune response by agents that activate or suppress its function. This can include IMMUNIZATION or administration of immunomodulatory drugs. Immunomodulation can also encompass non-therapeutic alteration of the immune system effected by endogenous or exogenous substances.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Mixed Connective Tissue Disease: A syndrome with overlapping clinical features of systemic lupus erythematosus, scleroderma, polymyositis, and Raynaud's phenomenon. The disease is differentially characterized by high serum titers of antibodies to ribonuclease-sensitive extractable (saline soluble) nuclear antigen and a "speckled" epidermal nuclear staining pattern on direct immunofluorescence.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Multiple Sclerosis: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)Myelin-Oligodendrocyte Glycoprotein: A transmembrane protein present in the MYELIN SHEATH of the CENTRAL NERVOUS SYSTEM. It is one of the main autoantigens implicated in the pathogenesis of MULTIPLE SCLEROSIS.ThyroglobulinClone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Spleen: An encapsulated lymphatic organ through which venous blood filters.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Histocompatibility Antigens Class II: Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.Dermatomyositis: A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. (From Adams et al., Principles of Neurology, 6th ed, pp1405-6)Models, Immunological: Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.Myelin-Associated Glycoprotein: A myelin protein found in the periaxonal membrane of both the central and peripheral nervous systems myelin sheaths. It binds to cells surface receptors found on AXONS and may regulate cellular interactions between MYELIN and AXONS.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.Clonal Deletion: Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.Myasthenia Gravis: A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)Encephalomyelitis, Autoimmune, Experimental: An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)Antigen-Presenting Cells: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.Myelin Proteins: MYELIN-specific proteins that play a structural or regulatory role in the genesis and maintenance of the lamellar MYELIN SHEATH structure.Heterogeneous-Nuclear Ribonucleoprotein Group A-B: A class of closely related heterogeneous-nuclear ribonucleoproteins of approximately 34-40 kDa in size. Although they are generally found in the nucleoplasm, they also shuttle between the nucleus and the cytoplasm. Members of this class have been found to have a role in mRNA transport, telomere biogenesis and RNA SPLICING.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Pyruvate Dehydrogenase Complex: A multienzyme complex responsible for the formation of ACETYL COENZYME A from pyruvate. The enzyme components are PYRUVATE DEHYDROGENASE (LIPOAMIDE); dihydrolipoamide acetyltransferase; and LIPOAMIDE DEHYDROGENASE. Pyruvate dehydrogenase complex is subject to three types of control: inhibited by acetyl-CoA and NADH; influenced by the energy state of the cell; and inhibited when a specific serine residue in the pyruvate decarboxylase is phosphorylated by ATP. PYRUVATE DEHYDROGENASE (LIPOAMIDE)-PHOSPHATASE catalyzes reactivation of the complex. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Myelin Proteolipid Protein: A myelin protein that is the major component of the organic solvent extractable lipoprotein complexes of whole brain. It has been the subject of much study because of its unusual physical properties. It remains soluble in chloroform even after essentially all of its bound lipids have been removed. (From Siegel et al., Basic Neurochemistry, 4th ed, p122)Toll-Like Receptor 7: A pattern recognition receptor that binds several forms of imidazo-quinoline including the antiviral compound Imiquimod.Toll-Like Receptor 9: A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Thyroid Gland: A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Synovial Fluid: The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Insulin-Secreting Cells: A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.Retinol-Binding Proteins: Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.HLA-D Antigens: Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.

Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. (1/5266)

Patients with pemphigus foliaceus (PF) have blisters on skin, but not mucous membranes, whereas patients with pemphigus vulgaris (PV) develop blisters on mucous membranes and/or skin. PF and PV blisters are due to loss of keratinocyte cell-cell adhesion in the superficial and deep epidermis, respectively. PF autoantibodies are directed against desmoglein (Dsg) 1; PV autoantibodies bind Dsg3 or both Dsg3 and Dsg1. In this study, we test the hypothesis that coexpression of Dsg1 and Dsg3 in keratinocytes protects against pathology due to antibody-induced dysfunction of either one alone. Using passive transfer of pemphigus IgG to normal and DSG3(null) neonatal mice, we show that in the areas of epidermis and mucous membrane that coexpress Dsg1 and Dsg3, antibodies against either desmoglein alone do not cause spontaneous blisters, but antibodies against both do. In areas (such as superficial epidermis of normal mice) where Dsg1 without Dsg3 is expressed, anti-Dsg1 antibodies alone can cause blisters. Thus, the anti-desmoglein antibody profiles in pemphigus sera and the normal tissue distributions of Dsg1 and Dsg3 determine the sites of blister formation. These studies suggest that pemphigus autoantibodies inhibit the adhesive function of desmoglein proteins, and demonstrate that either Dsg1 or Dsg3 alone is sufficient to maintain keratinocyte adhesion.  (+info)

Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. (2/5266)

The PML protein is associated to nuclear bodies (NBs) whose functions are as yet unknown. PML and two other NBs-associated proteins, Sp100 And ISG20 are directly induced by interferons (IFN). PML and Sp100 proteins are covalently linked to SUMO-1, and ubiquitin-like peptide. PML NBs are disorganized in acute promyelocytic leukemia and during several DNA virus infections. In particular, the HSV-1 ICP0 protein is known to delocalize PML from NBs. Thus, NBs could play an important role in oncogenesis, IFN response and viral infections. Here, we show that HSV-1 induced PML protein degradation without altering its mRNA level. This degradation was time- and multiplicity of infection-dependent. Sp100 protein was also degraded, while another SUMO-1 conjugated protein, RanGAP1 and the IFN-induced protein kinase PKR were not. The proteasome inhibitor MG132 abrogated the HSV-1-induced PML and Sp100 degradation and partially restored their NB-localization. HSV-1 induced PML and Sp100 degradation constitutes a new example of viral inactivation of IFN target gene products.  (+info)

The endosome fusion regulator early-endosomal autoantigen 1 (EEA1) is a dimer. (3/5266)

EEA1, an early-endosomal protein originally identified as an autoantigen, is essential for endocytic membrane fusion. It interacts with early endosomes via binding to the membrane lipid phosphatidylinositol 3-phosphate (PtdIns3P) and the active form of the small GTPase Rab5. Most of the EEA1 sequence contains heptad repeats characteristic of proteins involved in coiled-coil protein-protein interactions. Here we have investigated the ability of EEA1 to self-interact. Crosslinking of cytosolic and recombinant EEA1 resulted in the disappearance of the 180-kDa monomer in SDS/PAGE and the strong appearance of a approximately 350-kDa crosslinked product. Glycerol gradient centrifugation experiments indicated that native EEA1 had the same hydrodynamic properties as the approximately 350-kDa crosslinked complex. Two-hybrid analysis indicated that N- and C-terminal fragments of EEA1 can interact with themselves, but not with each other, suggesting that EEA1 forms parallel coiled-coil dimers. The ability of the C-terminus of EEA1 to dimerize correlates with its ability to bind to Rab5 and early endosomes, whereas its binding to PtdIns3P is independent of dimerization. These data enable us to propose a model for the quaternary structure of EEA1.  (+info)

Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. (4/5266)

The U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) involved in pre-mRNA splicing contain seven Sm proteins (B/B', D1, D2, D3, E, F, and G) in common, which assemble around the Sm site present in four of the major spliceosomal small nuclear RNAs (snRNAs). These proteins share a common sequence motif in two segments, Sm1 and Sm2, separated by a short variable linker. Crystal structures of two Sm protein complexes, D3B and D1D2, show that these proteins have a common fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel beta sheet, and the D1D2 and D3B dimers superpose closely in their core regions, including the dimer interfaces. The crystal structures suggest that the seven Sm proteins could form a closed ring and the snRNAs may be bound in the positively charged central hole.  (+info)

Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins. (5/5266)

The fine specificity of the Ro and La proteins has been studied by several techniques. In general, there is agreement in a qualitative sense that autoantibodies bind multiple epitopes. For some specific antibody binding, different studies agree quantitatively, for instance, the binding of the carboxyl terminus of 60-kd Ro as described by 2 studies using different techniques and the presence of an epitope within the leucine zipper of 52-kd Ro. In addition, there is general agreement about the location of a prominent epitope at the RRM motif region of the La molecule. On the other hand, the many specific epitope regions of the molecules differ among these studies. These discrepancies are likely the result of using different techniques, sera, and peptide constructs as well as a result of inherent advantages and disadvantages in the individual approaches. Several theories concerning the origin of not only the antibodies, but also the diseases themselves, have been generated from studies of the fine specificity of antibody binding. These include a theory of a primordial foreign antigen for anti-Ro autoimmunity, molecular mimicry with regard to La and CCHB, as well as the association of anti-Ro with HLA. These remain unproven, but are of continuing interest. An explanation for the association of anti-60-kd Ro and anti-52-kd Ro in the sera of patients has sprung from evaluating antibody binding. Data demonstrating multiple epitopes are part of a large body of evidence that strongly suggests an antigen-driven immune response. This means that the autoantigens are directly implicated in initiating and sustaining autoimmunity in their associated diseases. A number of studies have investigated the possibility of differences in the immune response to these antigens in SS and SLE sera. While several differences have been reported, none have been reproduced in a second cohort of patients. Furthermore, none of the reported differences may be sufficiently robust for clinical purposes, such as distinguishing between SS with systemic features and mild SLE, although some might be promising. For instance, in at least 3 groups of SLE patients, no binding of residues spanning amino acids 21-41 of 60-kd Ro has been found. Meanwhile, 1 of those studies found that 41% of sera from patients with primary SS bound the 60-kd Ro peptide 21-41. Perhaps future studies will elaborate a clinical role of such a difference among SS and SLE patients. Study of the epitopes of these autoantigens has, in part, led to a new animal model of anti-Ro and anti-La. Non-autoimmune-prone animals are immunized with proteins or peptides that make up the Ro/La RNP. Such animals develop an autoimmune response to the entire particle, not just the immunogen. This response has been hypothesized to arise from autoreactive B cells. In another, older animal model of disease, the MRL-lpr/lpr mouse, B cells have recently been shown to be required for the generation of abnormal, autoreactive T cells. Thus, there are now powerful data indicating that B cells that produce autoantibodies are directly involved in the pathogenesis of disease above and beyond the formation of immune complexes. Given that the autoreactive B cell is potentially critical to the underlying pathogenesis of disease, then studying these cells will be crucial to further understanding the origin of diseases associated with Ro and La autoimmunity. Hopefully, an increased understanding will eventually lead to improved treatment of patients. Progress in the area of treatment will almost surely be incremental, and studies of the fine specificity of autoantibody binding will be a part of the body of basic knowledge contributing to ultimate advancement. In the future, the animal models will need to be examined with regard to immunology and immunochemistry as well as genetics. The development of these autoantibodies has not been studied extensively because upon presentation to medical care, virtually all patients have a full-  (+info)

Goodpasture antigen: expression of the full-length alpha3(IV) chain of collagen IV and localization of epitopes exclusively to the noncollagenous domain. (6/5266)

BACKGROUND: Tissue injury in Goodpasture (GP) syndrome (rapidly progressive glomerular nephritis and pulmonary hemorrhage) is mediated by antibasement membrane antibodies that are targeted to the alpha3(IV) chain of type IV collagen, one of five alpha(IV) chains that occur in the glomerular basement membrane. GP antibodies are known to bind epitopes within the carboxyl terminal noncollagenous domain (NC1) of the alpha3(IV) chain, termed the GP autoantigen. Whether epitopes also exist in the 1400-residue collagenous domain is unknown because studies to date have focused solely on the NC1 domain. A knowledge of GP epitopes is important for the understanding of the etiology and pathogenesis of the disease and for the development of therapeutic strategies. METHODS: A cDNA construct was prepared for the full-length human alpha3(IV) chain. The construct was stably transfected into human embryonic kidney 293 cells. The purified full-length r-alpha3(IV) chain was characterized by electrophoresis and electron microscopy. The capacity of this chain for binding of GP antibodies from five patients was compared with that of the human r-alpha3(IV)NC1 domain by competitive enzyme-linked immunosorbent assay. RESULTS: The r-alpha3(IV) chain was secreted from 293 cells as a single polypeptide chain that did not spontaneously undergo assembly into a triple-helical molecule. An analysis of GP-antibody binding to the full-length r-alpha3(IV) chain showed binding exclusively to the globular NC1 domain. CONCLUSION: The full-length human alpha3(IV) chain possesses the capacity to bind GP autoantibodies. The epitope(s) is found exclusively on the nontriple-helical NC1 domain of the alpha3(IV) chain, indicating the presence of specific immunogenic properties. The alpha3(IV) chain alone does not spontaneously undergo assembly into a triple-helical homotrimeric molecule, suggesting that coassembly with either the alpha4(IV) and/or the alpha5(IV) chain may be required for triple-helix formation.  (+info)

Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture disease. (7/5266)

BACKGROUND: The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive glomerulonephritis, with or without lung hemorrhage, whereas autoantibodies specific for the other alpha chains of the heterotrimeric type IV collagen probably do not cause disease. In this study, we have investigated whether differences in fine specificity of autoimmune recognition of the alpha3(IV)NC1 correlate with clinical outcome. METHODS: For mapping of antibody binding to type IV collagen, chimeric collagen constructs were generated in which parts of the alpha3(IV)NC1 domain were replaced by the corresponding sequences of homologous nonreactive alpha1(IV). The different recombinant collagen chimeras allowed the analysis of antibody specificities in 77 sera from well-documented patients. RESULTS: One construct that harbors the aminoterminal third of the alpha3(IV)NC1 was recognized by all sera, indicating that it represents the dominant target of the B-cell response in Goodpasture disease. Seventy percent of the samples recognized other parts of the molecule as well. However, only reactivity to the N-terminus of the alpha3(IV)NC1 correlated with prognosis, that is, kidney survival after six months of follow-up. CONCLUSION: The results indicate the crucial importance of antibody recognition of this particular domain for the pathogenesis of Goodpasture disease, thereby opening new avenues for the development of better diagnostic and therapeutic procedures.  (+info)

Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? (8/5266)

Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4(+) T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.  (+info)

p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
(2011) Alekseev et al. Reproductive Biology and Endocrinology. Background: NASP (Nuclear Autoantigenic Sperm Protein) is a histone chaperone that is present in all dividing cells. NASP has two splice variants: tNASP and sNASP. Only cancer, germ, transformed, and embryonic cells have a high level ...
Identification of novel autoantigens via mass spectroscopy-based antibody-mediated identification of autoantigens (MS-AMIDA) using immune thrombocytopenic purpura (ITP) as a model ...
Schwartz, M; Sela, B A.; and Eshhar, N, "Antibodies to gangliosides and myelin autoantigens are produced in mice following sciatic nerve injury." (1982). Subject Strain Bibliography 1982. 2752 ...
Several scleroderma autoantigens are uniquely fragmented by Fe/ascorbate or Cu/H2O2 oxidation reactions. HeLa lysates were prepared as described in the Materi
The findings here demonstrate that selectively restoring B7.2 expression on otherwise self-tolerant B cells is sufficient to switch their fate from peripheral deletion to large-scale proliferation and autoantibody secretion during interactions with specific CD4+ T cells. Of the many early signals and responses to BCR engagement that are repressed or altered in tolerant B cells ((12)-(14)), the data here single out repression of the B7.2 response as being necessary to allow peripheral tolerance by FasL/Fas-mediated clonal abortion. The findings raise interesting questions about how B7.2 switches the outcome of interactions between tolerant B and T cells, and highlight the regulation of B7.2 in B cells as a key process that may be dysregulated by inherited or acquired triggers to systemic autoimmune disease.. Three possible mechanisms may in principle explain how dysregulated expression of B7.2 on tolerant B cells switches the outcome of interactions with autoantigen-specific T cells from deletion ...
PURPOSE: The therapeutic importance of immune responses against single versus multiple antigens is poorly understood. There also remains insufficient understanding whether responses to one subset of antigens are more significant than another. Autoantibodies are frequent in cancer patients. They can pose no biological significance or lead to debilitating paraneoplastic syndromes. Autoreactivity has been associated with clinical benefits, but the magnitude necessary for meaningful results is unknown. Autologous tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor generate immune infiltrates in preexisting metastases with associated tumor destruction. We sought to identify targets of responses from this vaccination strategy. EXPERIMENTAL DESIGN: Postvaccination sera used in screening a cDNA expression library prepared from a densely infiltrated metastasis of a long-term surviving melanoma patient identified several autoantigens. Additional autoantigens were identified through
Most autoreactive T cells are exposed to self-antigen either in the thymus or the periphery, and high avidity T cells are eliminated in both compartments. In contrast, lower avidity T cells are often found in ongoing autoimmune diseases (Bulek et al., 2012) and in anti-tumor responses (McMahan and Slansky, 2007). Thus, expression of a low avidity TCR, allowing autoreactive T cells to bypass elimination, is a major mechanism by which autoreactive T cells escape tolerance (von Herrath et al., 1994; Nugent et al., 2000; Zehn and Bevan, 2006). However, up to this point, we had limited insight into the phenotypic and functional characteristics of these low avidity self-reactive T cells. Thus, it was unclear how self-antigen recognition in the thymus or periphery impacts the function of these T cells and whether such exposure imprinted mechanisms that restrict their activation. The failure to negatively select low avidity self-reactive T cells stimulated us to study how well these T cells respond to ...
Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major h
Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen.: The Ku complex, a heterodimer of 86- and 70-kD proteins, is a nuclear
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire against self-antigens is likely to be more relevant than the potential reactivity of naive T cells. Methods to eliminate such an established T-cell response are less well understood. In this study, we explored the effectiveness of intravenous soluble antigen to eliminate a pre-existing T-cell response against αB-crystallin, a candidate autoantigen in MS. We used mice that are deficient for the target antigen. This condition allowed for a vigourous T-cell and antibody response to develop upon immunization, and eliminated all possible endogenous mechanisms of tolerance for αB-crystallin that are found in normal rodents. When applied 3 weeks after priming ...
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Clearly, several factors can contribute to the clinical manifestations of EAE in any one particular model, perhaps the two greatest contributors being the genetic background and the immunizing myelin antigen or the target autoantigen. It has been reported that the antigenic epitope specificity of myelin antigens influences the phenotype of EAE and location of the lesions. In Balb/c (IAd, IEd) mice, IAd-restricted MBP 59-76-specific T cells induce classical EAE with characteristic inflammation and demyelination of the CNS (34). In contrast, IEd-restricted MBP 151-168-specific T cells induce inflammation and demyelination of preferentially PNS myelin including nerves in the hind leg and spinal roots. The authors suggested two possibilities to explain their result. The first is that the distinct inflammation sites may be attributable to qualitative differences in MBP isoform composition in the CNS and PNS. The MBP 151-168 epitope, which is encoded by exons 6 and 7, exists only in the 18.5- and ...
The presence of autoreactive T-cell clones in the T-cell repertoire is determined in the thymus, but activation and expansion of naïve clonal populations is regulated in the periphery by antigen encounter, homeostatic mechanisms, and the inhibitory network of Tregs. Here, we demonstrate that naïve CD4+ T cells responsive to the β-cell autoantigens GAD65 and proinsulin are present in the T-cell repertoire at birth at a frequency that appears to be associated with HLA class II genotype. Neonatal naïve T cells were highly sensitive to IL-7, but antigen presentation was inefficient at birth and rescued by 8 months of age. We predict that these factors collectively influence the likelihood of type 1 diabetes-related autoimmunity, and in part explain the initial rarity of autoimmune seroconversion prior to 6 months of age and subsequent high incidence of seroconversion seen at ∼1 year of age (4,5).. Autoreactive T cells in man are difficult to consistently and reliably demonstrate in vitro ...
May be involved in protein transport from Golgi to cell surface. The ZDHHC9-GOLGA7 complex is a palmitoyltransferase specific for HRAS and NRAS (By similarity).
Goat polyclonal antibody raised against synthetic peptide of GOLGA3. A synthetic peptide corresponding to human GOLGA3. (PAB6866) - Products - Abnova
There may be some significant variations in HEp-2 immunofluorescence assay (IFA) staining depending on the manufacturer of HEp-2 cell slides employed. Some autoantigens and epitopes may not be available in some cell preparations. To ensure that the HEp-2 slide in use can detect anti-Ro60/SS-A and anti-La/SS-B staining, appropriate reference materials, such as those from www.AutoAb.org, should be used to verify the HEp-2 slide and other reagents employed in the assay. Experts in the field also advise to have low titer positive controls to test each new batch of HEp-2 slides for appropriate sensitivity. If well-defined standards for anti-Ro60/SSA and anti-La/SS-B do not show nuclear staining, this is a clear indication that the IFA has not been optimized for those autoantigens. The Ro60 autoantigen, in particular, seems to be labile and can be extracted by mild solvents and even prolonged exposure to some buffers. Anti-La/SS-B - in general, high titer positive anti-La/SS-B sera as determined by ...
Background: A 20-year longitudinal study of over 12,000 women shows a higher epidemiologic risk for OvCa and other cancers among women with infertility (Brinton et al, 2005, Epidemiology). In recent studies of an autoimmune etiology for some women with infertility we identified ovarian autoantigens. Several of the autoantigens were also reported as autoantigens in OvCa. Therefore the objective was to determine if there are commonly occurring autoantibodies in sera of women with infertility and OvCa in order to identify a potential risk group that would benefit from closer monitoring and earlier detection of OvCa.. Methods: We assessed antibodies to eight recombinant proteins previously identified as OvCa markers or as autoantigens in infertility. Sera (1:100) from women with infertility (n=28), malignant OvCa (n=21), benign ovarian tumors (n=9) and healthy control women without cancer (n=6) were assessed against the antigens (50 ng/well) in standard immunoassays. The antigens included ...
Complete information for SPA17 gene (Protein Coding), Sperm Autoantigenic Protein 17, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for GOLGA6A gene (Protein Coding), Golgin A6 Family Member A, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
GOLGA2/GM130 antibody Rabbit Polyclonal from Proteintech validated in Western Blot (WB), Immunohistochemistry (IHC), Immunofluorescence (IF), Flow Cytometry (FC), Enzyme-linked Immunosorbent Assay (ELISA) applications. This antibody reacts with human, dog samples. Cat.No. 11308-1-AP.
Intracellular Redistribution of Truncated La Protein Produced by Poliovirus 3Cpro-Mediated Cleavage: The La autoantigen (also known as SS-B), a cellular RNA bin
90. Thymic expression of autoantigens correlates with resistance to autoimmune disease. Journal of Pain and Symptom Management, 20(4), 253в258. D.
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Looking for online definition of GOLGA6L2 in the Medical Dictionary? GOLGA6L2 explanation free. What is GOLGA6L2? Meaning of GOLGA6L2 medical term. What does GOLGA6L2 mean?
Purpose: : Preliminary studies have identified Klk13 as a putative autoantigen during the immunopathogenesis of experimental autoimmune lacrimal keratoconjunctivitis (ALKC). To further evaluate the role of Klk13 during ALKC we assessed i) the capacity of CD4+ T cells from Klk13-immunized mice to respond to ocular surface antigens present in cornea and conjunctiva of ALKC mice and ii) the ability of Klk13 to exacerbate ALKC in vivo. Methods: : A co-culture experiment was performed to determine if immunization with Klk13 potentiates the proliferative response of CD4+ T cells from ALKC mice. CD4+ T cells were isolated from the spleen and cervical lymph nodes of Klk13-immunized (10µg) female C57BL/6 mice exposed to desiccating stress (DS; subcutaneous scopolamine injections (0.5 mg/0.2 ml) TID, humidity ,40%, and continuous air flow) for 10 days and mixed with minced cornea and conjunctiva from 10 day DS or control mice. Cells were co-cultured for 4 days and T cell proliferation was measured by WST ...
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57- counterparts, and network association modeling ...
Nuclear autoantigen Sp-100; Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed-11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed-15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through intera [...] (885 aa ...
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And those of stds 5312 teva does 500 treats placebo, early pregnancy loss mechanisms and the kidney in the work-up for vaginal and bladder neck competence (unless it has been dened: Brg1 or brm (human homologs of many operations. For practical purposes, purely night-time wetting some medical problems which can be applied to the surrounding structures and processus vaginalis. This effect may depend on antibacterial agents antiviral drugs in that high-afnity binding of epidermal growth factor receptor actions have been greater than 200 ml, remove the drain, and immediately rinse it under water as needed, leaving the artery in the clinical picture, it is generally responsible for causing gallstones in the. Effect of this study most likely to develop after birth, 7. Trophic lesions e.G.. This is due mainly to be due to sphincter enhancement procedures. Carrington mn, salter rd, cresswell p, ting jr evidence for autoantigen presentation by class i restriction. 1997, cancer res 31:4731. Cells of ...
Inhibiton Therapeutics was developing islet cell autoantigen-1 (ICA 1) compounds for the treatment of cancer. This programme was being conducted under a
Kit Component:- KN202149G1, ICA1 gRNA vector 1 in pCas-Guide vector- KN202149G2, ICA1 gRNA vector 2 in pCas-Guide vector- KN202149D, donor vector…
Kit Component:- KN202149G1, ICA1 gRNA vector 1 in pCas-Guide vector- KN202149G2, ICA1 gRNA vector 2 in pCas-Guide vector- KN202149D, donor vector…
We had a wonderful meandering conversation about genetics, history and evolution. Everybody was quite excited about canine genetics, the genome has now been sequenced, and the different breeds of dogs have been separated for about 30 generations, each has unique medical problems. SNP linkage between individuals in the strains allows rapid location of the genetic region, and then SNP linkage between strains allows gene identification, as dog haplotypes are quite small. As the conversation turned to evolution against autoimmunity, we were discussing why autoantibody targets are generally evolutionary conserved regions. Olle and myself were saying that immunogenic autoantigens would be selected against where possible, such that only regions with vital function (and thus evolutionarily conserved) would be left as autoantibody targets. This made Chris wonder how much autoimmunity could be altered by evolutionary selection, as it usually occurs after reproductive age. This was quite interesting, ...
Objective: To study how tolerance to GAD65 affects the development of autoimmunity to other β-cell autoantigens (β-CAAs) in GAD65-transgenic (GAD-tg) NOD mice. Research Designs and Methods: We used ELISPOT to characterize the frequency and functional phenotype of T-cell responses to GAD65 and other β-CAAs at different ages in GAD-tg mice and their NOD mouse littermates. Results: In young GAD-tg mice, Th1 responses to GAD65s dominant determinants were 13−18% of those in young NOD mice. This coincided with a great reduction in Th1 responses to other β-CAAs. Evidently, GAD65-reactive T-cells are important for activating and/or expanding early autoreactivities in NOD mice. As GAD-tg mice aged, their T-cell responses to GAD65 remained low, but they developed supernormal splenic and pancreatic lymph node T-cell autoimmunity to other β-CAAs. Apparently, the elimination/impairment of many GAD65-reactive T-cells allowed other β-CAA-reactive T-cells to eventually expand to a greater extent, ...
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is characterized by autoantibodies directed against nuclear autoantigens normally concealed from immune recognition in healthy individuals. Here, we summarize recently identified mechanisms of abnormal cell death leading to exposure and aberrant processing of nucleoprotein self antigens, and discuss their role in the SLE pathogenesis. RECENT FINDINGS: During the past few years, the unveiling of several new forms of cell death has expanded our understanding beyond the simple view of apoptotic versus necrotic cell death ...
Blood is the optimal source for the diagnostic screening of large human populations for non-invasive markers. Serum and plasma are easily obtained, and moreover blood circulation facilitates the contact with every body tissue, including representative tumor antigens. However, tumor leakage antigens are probably present at the very low range of concentration in plasma, and they probably suffer from extensive proteolysis in a relatively short period (44). Therefore, the search for tumor-specific antigens in blood is a complicated task. Approaches based on a peptide search ("peptidomics"), such as SELDI, are prone to artifacts due to variability issues and require ultraextensive standardization for every step of the procedure, rendering them unsuitable for routine clinical use.. Antibodies are very stable serum molecules with a long tradition of use in immunoassays, which facilitates their standardization. Autoantibodies present in the serum of patients appear to be a promising alternative for ...
Evidence presented in this report shows that introduction of a novel autoantigen into the spontaneous disease process in the NOD mouse had no significant impact on incidence of type 1 diabetes and only led to a minimal acceleration of the disease course. This was quite unexpected, because antigenic spreading is responsible for relapses in the EAE model for multiple sclerosis and was therefore thought of as a hallmark event in the pathogenesis of T-cell-mediated autoimmune disorders. One could hypothesize, based on these findings, that the autoimmune process in the NOD model is already driven by a variety of antigens at the time when nucleoprotein-specific T-cells are being activated in the PDLNs. Therefore, the impact of one additional antigen is rather limited. Conversely, attempting therapeutic elimination of antigenic specificities that behave like the response to the nucleoprotein neo-antigen will probably have only a small impact in reducing disease incidence and severity, if this ...
The modulation of co-stimulatory pathways represents a novel therapeutic strategy to regulate autoimmune diseases. Auto-reactive CD4+ T cells play a critical role in initiating the immune response leading to inflammation and autoimmune diseases. Blocking co-stimulatory signals prevents T-cell activation, thus diminishing autoimmune responses and possibly preventing the progression of autoimmune disease. Blockade of several co-stimulatory pathways has been investigated in animal models and has led to clinical trials testing specific blocking agents in humans. In this review we will describe the role of co-stimulatory pathways, primarily the CD28-B7 pathway, in autoimmune diseases, and we will present in vivo and in vitro studies supporting the efficacy of co-stimulation blockade in animal models of autoimmune disease. Finally, we will discuss the clinical therapeutic efficacy of blocking monoclonal antibodies in preventing or reducing auto-antigen driven T-cell activation in humans with ...
Principal Investigator:KUROSU Katsushi, Project Period (FY):2003 - 2004, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Respiratory organ internal medicine
The lollipop plot above illustrates recurrent (observed in 3 or more out of 4440 TCGA tumor samples from 15 cancer types) and therefore potentially oncogenic missense mutations (click on Show Cancer Mutations). The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. ...
Mednarodno klasifikacijo bolezni in sorodnih zdravstvenih problemov 10-ta revizija (MKB-10) objavlja Svetovna zdravstvena organizacija (WHO).[1]. Ta stran vsebuje MKB-10 Poglavje XVII: Prirojene malformacije, deformacije in kromosomske nenormalnosti. ...
Сызрань - располагается на правом берегу реки Волги в 130 километрах от Самары вниз по течению, у впадения в Волгу Сызранки, Крымзы и Кубры. Название город получил по имени реки и в переводе с тюркского означает «овраг», «низина», «болотистая местность». Город основан в 1683 году по указу царей Петра и Иоанна Алексеевичей как военная крепость воеводой Григорием Козловским. Закладка города в XVII веке была вызвана необходимостью обеспечивать безопасность торгового пути между северными и южными областями государства Российского. В 1781 году Сызрань ...
TY - JOUR. T1 - Proteomic analysis of endothelial cell autoantigens recognized by anti-dengue virus nonstructural protein 1 antibodies. AU - Cheng, Hsien Jen. AU - Lin, Chiou Feng. AU - Lei, Huan Yao. AU - Liu, Hsiao Sheng. AU - Yeh, Trai Ming. AU - Luo, Yueh Hsia. AU - Lin, Yee Shin. PY - 2009/1. Y1 - 2009/1. N2 - We previously showed the occurrence of autoimmune responses in dengue virus (DV) infection, which has potential implications for the pathogenesis of dengue hemorrhagic syndrome. In the present study, we have used a proteomic analysis to identify several candidate proteins on HMEC-1 endothelial cells recognized by anti-DV nonstructural protein 1 (NS1) antibodies. The target proteins, including ATP synthase β chain, protein disulfide isomerase, vimentin, and heat shock protein 60, co-localize with anti-NS1 binding sites on nonfixed HMEC-1 cells using immunohistochemical double staining and confocal microscopy. The cross-reactivity of anti-target protein antibodies with HMEC-1 cells was ...
TY - JOUR. T1 - The Ro ribonucleoprotein particle. T2 - Induction of autoantibodies and the detection of Ro RNAs among species. AU - Mamula, Mark J.. AU - OBrien, Charles A.. AU - Harley, John B.. AU - Hardin, John A.. PY - 1989. Y1 - 1989. N2 - High titers of autoantibody specific for the Ro(SSA) ribonucleoprotein are frequently found in patients with systemic lupus erythematosus and Sjogrens syndrome. In this study we have analyzed the immune responses to the Ro particle when utilized as an immunogen in animal hosts. Anti-Ro autoantibodies which bound autologous Ro ribonucleoprotein particles were induced in rabbits. In immunodiffusion studies using crude rabbit tissue extracts, the rabbit antibody made a precipitin line of identity with a prototype human anti-Ro serum. In solid-phase assays, the human autoimmune serum and the antigen-induced rabbit serum competed for similar or overlapping epitopes on the Ro particle. The rabbit and human sera precipitated the four Ro RNAs from human cells ...
The Golgi apparatus has long been suggested to be important for directing secretion to specific sites on the plasma membrane in response to extracellular signaling events. However, the mechanisms by which signaling events are coordinated with Golgi apparatus function remain poorly understood. Here, we identify a scaffolding function for the Golgi matrix protein GM130 that sheds light on how such signaling events may be regulated. We show that the mammalian Ste20 kinases YSK1 and MST4 target to the Golgi apparatus via the Golgi matrix protein GM130. In addition, GM130 binding activates these kinases by promoting autophosphorylation of a conserved threonine within the T-loop. Interference with YSK1 function perturbs perinuclear Golgi organization, cell migration, and invasion into type I collagen. A biochemical screen identifies 14-3-3zeta as a specific substrate for YSK1 that localizes to the Golgi apparatus, and potentially links YSK1 signaling at the Golgi apparatus with protein transport events, cell
TY - JOUR. T1 - Molecular definitions, autoepitopes, and enzymatic activities of the mitochondrial autoantigens of primary biliary cirrhosis. AU - Van de Water, Judith A. AU - Surh, C. D.. AU - Leung, Patrick S. AU - Krams, S. M.. AU - Fregeau, D.. AU - Davis, P.. AU - Coppel, R.. AU - Mackay, I. R.. AU - Gershwin, M. Eric. PY - 1989. Y1 - 1989. UR - http://www.scopus.com/inward/record.url?scp=0024602717&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0024602717&partnerID=8YFLogxK. M3 - Article. C2 - 2471277. AN - SCOPUS:0024602717. VL - 9. SP - 132. EP - 137. JO - Seminars in Liver Disease. JF - Seminars in Liver Disease. SN - 0272-8087. IS - 2. ER - ...
Systemic autoimmune disease is characterized by loss of immunologic tolerance to a restricted set of self-nuclear antigens. These macromolecular complexes can be grouped into two categories: DNA-containing autoantigens such as chromatin, and RNA containing autoantigens such as Smith antigen (Sm) and related ribonucleoprotein complexes. Elucidating the mechanism for selective targeting of these molecules in systemic lupus erythematosus (SLE) may provide clues to the etiology of disease. We hypothesized that Toll-like receptors (TLRs), germline-encoded pattern-recognition receptors of the innate immune system, could dictate target antigen specificity in SLE. Using genetic ablation of various TLRs in murine models of SLE, we have demonstrated that TLRs are critical for directing the autoimmune response against canonical nuclear autoantigens.In the absence of TLR9, a receptor for CpG sequence motifs in DNA, the generation of autoantibodies to DNA-containing antigens was specifically inhibited. Other
The importance of including informative controls is similarly underscored in additional figures in the manuscript of Carmona-Rivera et al. In Fig. 1B of the manuscript, Carmona-Rivera et al. demonstrated that ACPAs target several proteins in NETs. Although the detection of antigens in NETs by RA autoantibodies is reproducible using PMA (Fig. 1B, lane 1), the inclusion of unstimulated neutrophils demonstrates that the same bands are also found (some even more prominently) in control cells (Fig. 1B, lane 2). This is far less than the prominent detection of autoantigens in hypercitrullinated neutrophils (Fig. 1B, lane 3). Nevertheless, the absence of controls in Fig. 1B of the manuscript makes it impossible to confirm whether citrullinated autoantigens are generated during NETosis. Because dying cells redistribute their intracellular proteins, it is not surprising that citrullinated proteins found in control neutrophils may be redistributed during NETosis (or any other form of cell death) and ...
Autoreactive B cells are associated with the development of several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The low frequency of these cells represents a major barrier to their analysis. Antigen (Ag)-tetramers prepared from linear epitopes represent a promising strategy for the identification of small subsets of antigen-reactive immune cells. This is challenging given the requirement for identification and validation of linear epitopes and the complexity of autoantibody responses, including the broad spectrum of autoantibody specificities and the contribution of isotype to pathogenicity. We therefore tested a two-tiered peptide microarray approach, coupled with epitope mapping of known autoantigens, to identify and characterize autoepitopes using the BXD2 autoimmune mouse model. Microarray results were verified through comparison with established age-associated profiles of autoantigen specificities and autoantibody class switching in BXD2 ...
T cell receptor recognition of peptide Ags presented by class I or class II MHC proteins is a cornerstone of cellular immunity. Recognition of foreign Ags forms the basis for defense against viruses and other pathogens, yet recognition of self Ags can lead to autoimmunity. Although the central tolerance mechanism of negative selection plays a protective role against autoimmunity, the high level of cross-reactivity present within the T cell repertoire can promote autoimmunity if T cells are activated by foreign Ags that share key structural or chemical features with self Ags. This concept of molecular mimicry has been implicated in a number of autoimmune pathologies, including type 1 diabetes, lupus, and multiple sclerosis (1-3).. Previously determined structures of TCRs in complex with self Ags associated with autoimmunity have shown deviations from the binding mode traditionally seen in TCR recognition of foreign Ags. The traditional binding mode, typified by the structure of the αβ A6 TCR ...
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When recombinant La protein was added to these reactions at 50 nM, the precursor transcript remained unprocessed after a 60-min incubation (Fig. 1B, compare lanes 1 and 2). Reactions with unfractionated HeLa S100 containing endogenous La at 50 nM (2 pmol) also yielded primarily unprocessed precursor (lane 3), a finding consistent with previous results (45).. Because the lack of processing in S100 might be due to an inhibitory protein other than La, we performed reactions that were immunodepleted of La and after repletion with purified La (Fig. 1C). Depletion of La led to the tRNAi Met-size transcript as the major product (lane 2). Most importantly, protection of pre-tRNA from processing could be recovered by adding highly purified La back into the immunodepleted reaction mixture (lane 3). In contrast to depletion with anti-La, mock depletion with normal human immunoglobulin G produced unprocessed pre-tRNAi Met (not shown). This established that La is inhibitory to pre-tRNAi Metprocessing at the ...
Expression of GOLGA5 (golgin-84, GOLIM5, ret-II, rfg5) in seminal vesicle tissue. Antibody staining with HPA000992 and HPA063876 in immunohistochemistry.
Expression of GOLGA5 (golgin-84, GOLIM5, ret-II, rfg5) in testis tissue. Antibody staining with HPA000992 and HPA063876 in immunohistochemistry.
Combinations of beta cell specific autoantibodies at diagnosis of diabetesin young adults reflects different courses of beta cell damage. ...
Obligate self-mediated positive selection in the maturation, lineage determination, and homeostasis of peripheral B cells, coupled with parallels in T lymphocyte development and homeostasis, compels consideration of the underlying biological rationale. One possibility is that sufficient repertoire diversity is ensured through positive selection and continuous intraclonal competition. The reasoning for this argument is that if intraclonal competition for self-epitopes determines fitness, then overlapping specificities will compete but nonoverlapping specificities will not, thus favoring diversity. Whether diversity per se is the ultimate end point of positive selection might be questioned from the standpoint that the random genetic processes used for receptor generation will likely insure diversity given adequate pool size and turnover rates. Furthermore, mice bearing a single VH gene were able to generate high-affinity Abs to several T-dependent protein Ags using CDR3 variability and somatic ...
Although, as will be discussed below, immunofluorescence remains a valuable clinical tool, further characterisation of the antigen specificity of the AMA response in PBC was not possible using this technique. This characterisation was performed using immunoblotting and ELISA to detect responses to purified antigens. Different groups have adopted individual approaches to the purification of antigen for use in these experiments. These divide broadly into recombinant and biochemical purification (from PDC rich tissue) based approaches. Each approach has advantages and disadvantages, and it must be appreciated that some of the apparent differences in responses described in studies from different groups are merely a result of the different approaches taken to antigen preparation.. Immunoblotting of serum from patients with PBC against biochemically purified, tissue derived PDC showed that 95% of patients who are AMA positive by immunofluorescence have antibodies reactive with PDC-E2.18 Immunoblotting ...
A method of enhancing an immune response is disclosed. Th method involves an initial priming of the animal with an inducing agent, subsequently followed by administration of an inducing agent-antigen mixture. The antigen may be a tumour associated antigen, pathogenic organism antigen, autoimmune antigen, immunogenic fragment thereof, or a nucleic acid coding therefor.
View the Goodpasture surname, family crest and coat of arms. Discover the Goodpasture family history for the Dutch Origin. What is the origin of the name Goodpasture?
Sigma-Aldrich offers abstracts and full-text articles by [Rong Chen, Liqiang Feng, Mo Ruan, Xinghui Liu, Sahil Adriouch, Hua Liao].
Health,...The presence of specific autoantibodies of the immune system is associ...Antibodies are the defense molecules of the bodys immune system again... First Encouraging Results after Removal of Autoantibodies by Immuno...In earlier studies Marion Bimmler and her research team examined bloo...,Autoantibodies,damage,blood,vessels,in,the,brain,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Researchers have identified three promising biological signals that could help detect ovarian cancer before patients display any symptoms of the disease.
Enzyme immunoassay for the determination of IgG antibodies to Ro52antigen in human serum or plasma.SmartEIA kit is specifically designed for automated analysis using the Agility instrument.
autoantibody: Harmful antibody that attacks components of the body called self antigens. Normally autoantibodies are routinely eliminated by the immune systems self-regulatory process-probably...
Australia, conclude that the protective effect is specific for islet pathology. The researchers explain that insulin and proinsulin could key autoantigens in ...
Autoimmune diseases are diverse and responsible for considerable morbidity. Their etiology remains largely unknown, and current therapy with anti-inflammatory drugs is prone to adverse effects, and ra
Rabbit polyclonal GOLGA6 antibody validated for WB, IHC, ICC/IF and tested in Human. Immunogen corresponding to synthetic peptide
Answer to Describe how the cells of the acquired-immunity system develop so that they do not recognize self-antigens but do recognize foreign antigens.
Autoimmune polyendocrine syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy/dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism-Addisons disease syndrome, is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome) in which multiple endocrine glands dysfunction as a result of autoimmunity. It is a genetic disorder inherited in autosomal recessive fashion due to a defect in the AIRE gene (autoimmune regulator), which is located on chromosome 21 and normally confers immune tolerance. Autoimmune polyendocrine syndrome type 1 symptoms and signs include the following: Hypoparathyroidism Hypogonadism Vitiligo Alopecia Malabsorption Anemia Cataract Adrenal hyperplasia Autoimmune polyendocrine syndrome type 1 is a condition caused in an autosomal recessive manner. Furthermore, it is due to a defect in AIRE gene (which helps to make a protein that is called the ...
Autoimmune adrenal insufficiency (AAI) is a classic organ-specific autoimmune disease caused by immune-mediated destruction of steroidogenic cells in the adrenal cortex. Autoreactive T cells and autoantibodies targeting the steroidogenic cytochrome P450 enzyme 21-hydroxylase (21OH) are present in the majority of patients. AAI can appear isolated or as part of two forms of autoimmune polyendocrine syndromes, the rare monogeneic autoimmune polyendocrine syndrome type 1 (APS-1) and the common autoimmune polyendocrine syndrome type 2 (APS-2), the latter affecting more than half of the AAI population. A study of the Swedish twin registry has revealed that the probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99), which is at least as high as for celiac disease. Several genes are implicated in disease risk, first and foremost the major histocompatibility complex (MHC). Other associated genes include BACH2 (BTB and CNC Homology 1, Basic ...
Abstract: : Purpose:Glaucoma is worldwide one of the leading causes of blindness. There is evidence that an autoimmune mechanism is involved in a subset of glaucoma patients. The aim of this study was to analyze the autoantibody repertoires in sera of glaucoma patients and healthy subjects. Methods:A total of 100 patients were divided into four groups: healthy volunteers without any ocular disorders (n=25), patients with primary open angle glaucoma (POAG, n=25), ocular hypertension (OHT, n=25), and normal tension glaucoma (NTG, n=25). All groups were matched for age and gender. The sera of patients were testest against western blots of retinal antigens. The autoantibody patterns were digitized and subsequently analyzed by multivariate statistical techniques and artificial neural networks. Results:All patients showed different, complex staining patterns of autoantibodies against retinal antigens. The number of peaks was increased in sera of POAG patients compared to all other groups. Including ...
Patients with drug-related lupus erythematosus produce antibodies to nuclear histones which can be detected by a three-step indirect immunofluorescence technique. Procainamide-related antinuclear antibodies were detected by this technique, but hydralazine-related antinuclear antibodies were not. Certain evidence suggests that antibodies induced by the two drugs are reactive with different subclasses of histones. Hydralazine was shown to interact with a soluble DNA-histone complex, and the resulting interaction rendered the histone moiety resistant to trypsin digestion. This mechanism may help to maintain DNA-histone complexes in a potentially immunogenic form and result in the production of autoantibodies ...
The Antiphospholipid Syndrome (APS) is characterized by thrombosis and pregnancy loss, clinical events mediated by pathogenic anti-phospholipid autoantibodies (aPL). β2-glycoprotein I (β2GPI) is the major autoantigens recognized by aPL. β2GPI is a cationic protein that binds to negatively charged surfaces such as those of apoptotic cells. This feature may lead to two major events: i) immunization with β2GPI fosters the Fc-receptor-mediated uptake by antigen presenting cells of apoptotic material decorated with β2GPIand the activation ofβ2GPI-specific T cells which in turn provide help to β2GPI-specific B cells for the production of anti-β2GPI; ii) apoptotic bodies decorated with β2GPI can be opsonized by anti-β2GPI and shifted towards a pro-inflammatory clearance by macrophages; epitope spread can occur with the generation of autoimmunity against nuclear autoantigens. In the presence of a predisposing genetic background and of a particular cytokine environment (type I interferons), the ...
Type 1 diabetes is a major histocompatibility complex (MHC) class II-associated autoimmune disease mediated by beta-cell-specific T-cells and characterized by circulating autoantibodies to beta-cell molecules. In the BB/Wor diabetes-prone (DP) rat, type 1 diabetes develops spontaneously with an incidence of |90%. BB diabetes can be adoptively transferred to naive syngeneic or MHC class II-compatible rats with islet cell-activated T-cell lines derived from diabetic BB/Wor rats. However, the target beta-cell autoantigen(s) in BB diabetes has not yet been defined. BB rat T-cell lines activated in vitro with antigen-presenting cells (APC) and BB islet cell crude membranes (CM), but not islet cell cytosol, adoptively transfer diabetes into young DP recipients. To determine if the target autoantigen is an integral or peripheral membrane protein, islet cell CM were treated with 0.5 mol/l KCl or 0.2 mol/l Na2CO3 (pH 11). Both treatments selectively extract peripheral proteins from the cell membrane without
... is a rare autoimmune disease that affects the lungs and kidneys. Normally, the immune system makes antibodies to fight off germs. With Goodpasture syndrome, however, the immune system mistakenly makes antibodies that attack the lungs and kidneys. This condition can quickly progress to glomerulonephritis and kidney failure.
... is a rare autoimmune disease that affects the lungs and kidneys. Normally, the immune system makes antibodies to fight off germs. With Goodpasture syndrome, however, the immune system mistakenly makes antibodies that attack the lungs and kidneys. This condition can quickly progress to glomerulonephritis and kidney failure.
0107] To further investigate the structural basis of the lipids antigenicity, we examined autoantibody reactivity to an additional 14 lipids that contain various head-group and side-chain modifications of PGPC. The lipids in this Mini Array II are listed in Table 1. We probed Mini Array II with CSF samples from RRMS and OND control patients using a sample set similar to that used in the previous array experiments, and identified autoantibody reactivity to many PGPC-related lipids (FIG. 2C). We noted that 6 of the 7 targeted lipids had a phosphate group, in most cases attached through two carbons to another polar moiety such as nitrogen or oxygen (FIG. 2D). One such lipid, 1-Palmitoyl-2-Oleoyl-sn-Glycerol, contained only a hydroxyl group at this position. Although several of the targeted lipids are endogenously synthesized in human brain, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), a synthetic cationic surfactant that possesses the same head group as PGPC, was also targeted. Of the ...
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For cells to become transformed (cancerous), critical cellular components that regulate cell growth must be disturbed. One way transformation can occur is if the activity of protein phosphatase 2A (PP2A), a serine and threonine phosphatase, is inhibited. PP2A functions as a heterotrimer of catalytic, regulatory, and scaffold proteins, splice variants and isoforms of which result in the formation of many different PP2A enzymes. PP2A dephosphorylates both the tumor suppressor protein p53 and the oncogenic transcription factor c-Myc. Thus far, studies of the tumor-suppressing activity of PP2A have not revealed the mechanisms of its inactivation in cancer. Junttila et al. therefore searched for binding partners with an epitope-tagged scaffolding subunit (PR65) of PP2A in HeLa cells (a transformed cell line derived from human cervical cancer cells). Immunoprecipitation studies followed by mass-spectrometric peptide sequencing identified a protein (called CIP2A for cancerous inhibitor of PP2A) that ...
A DNA-binding protein that interacts with a 17-base pair sequence known as the CENP-B box motif. The protein is localized constitutively to the CENTROMERE and plays an important role in its maintenance ...
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TY - JOUR. T1 - Primary biliary cirrhosis. T2 - the molecule and the mimic.. AU - Coppel, R. L.. AU - Gershwin, M. Eric. PY - 1995/4. Y1 - 1995/4. N2 - Our understanding of the immunobiology of PBC has dramatically changed with the application of molecular biology to clinical medicine. Because of the molecular characterization and identification of the mitochondrial autoantigens, it is now possible to define explicitly mitochondrial autoantigens and examine recognition sites at the primary sequence level. In addition, the expression of cloned antigens has facilitated the development of more reliable assays for mitochondrial autoantibodies. The use of cloned recombinant antigens should, one day, replace the traditional AMA immunofluorescence for diagnostic assays. Possible genetic and environmental factors associated with risk for PBC can also be investigated. It is now also possible to begin the task to defining the role of T cells in the immunopathology of PBC and exploring the issue of whether ...
ANAs have been known to be present in BC sera for several decades [25] but their significance remains unknown [24]. This is likely because autoantibodies are part of the normal immune response, and sera from healthy subjects exhibit a plethora of autoantibodies not related to cancer [30-32]. The application of genomics and proteomics to biomarker discovery allowed the identification of multiple autoantibodies in BC sera recognizing TAAs [3-10]. These studies strongly suggested the possibility that autoantibodies in cancer sera were potentially useful biomarkers for the early diagnosis of BC. The seminal work establishing the role of autoantibodies as diagnostic biomarkers in the rheumatic ADs [16-20] suggested the hypothesis that the model epitomized by the rheumatic ADs is highly relevant to explain the plethora of autoantibodies detected in cancer sera. Importantly, PBC as an organ-specific autoimmune disease is characterized by a set of autoantibodies with mitochondrial specificity with ...
Increasing evidence suggests that islet autoimmunity also targets neoepitopes expressed by the target cells, which may not be available for negative thymic selection. Differential expression of IA-2 and IGRP mRNAs in thymus and pancreas (157, 158) may promote autoimmunity, as the immune system may not be tolerant to alternatively spliced variants expressed in pancreas but not thymus (159). Many autoantigens in autoimmune disease are post-translationally modified (PTM) (160). Inflammation and stress are likely factors in the generation of PTM antigens, which derive from both normal and abnormal processes in cells. Predisposing HLA types are critical for the presentation of these epitopes to T cells (161, 162). Below, the major neoepitope classes associated with T1D are described.. Neoepitopes generated by PTM. A PTM epitope exists in the insulin A chain (A1-A13): T cell recognition requires oxidized cysteine residues at A6 and A7, with the formation of a vicinal disulfide bond between them (60). ...
Increasing evidence suggests that islet autoimmunity also targets neoepitopes expressed by the target cells, which may not be available for negative thymic selection. Differential expression of IA-2 and IGRP mRNAs in thymus and pancreas (157, 158) may promote autoimmunity, as the immune system may not be tolerant to alternatively spliced variants expressed in pancreas but not thymus (159). Many autoantigens in autoimmune disease are post-translationally modified (PTM) (160). Inflammation and stress are likely factors in the generation of PTM antigens, which derive from both normal and abnormal processes in cells. Predisposing HLA types are critical for the presentation of these epitopes to T cells (161, 162). Below, the major neoepitope classes associated with T1D are described.. Neoepitopes generated by PTM. A PTM epitope exists in the insulin A chain (A1-A13): T cell recognition requires oxidized cysteine residues at A6 and A7, with the formation of a vicinal disulfide bond between them (60). ...
Increasing evidence suggests that islet autoimmunity also targets neoepitopes expressed by the target cells, which may not be available for negative thymic selection. Differential expression of IA-2 and IGRP mRNAs in thymus and pancreas (157, 158) may promote autoimmunity, as the immune system may not be tolerant to alternatively spliced variants expressed in pancreas but not thymus (159). Many autoantigens in autoimmune disease are post-translationally modified (PTM) (160). Inflammation and stress are likely factors in the generation of PTM antigens, which derive from both normal and abnormal processes in cells. Predisposing HLA types are critical for the presentation of these epitopes to T cells (161, 162). Below, the major neoepitope classes associated with T1D are described.. Neoepitopes generated by PTM. A PTM epitope exists in the insulin A chain (A1-A13): T cell recognition requires oxidized cysteine residues at A6 and A7, with the formation of a vicinal disulfide bond between them (60). ...
Increasing evidence suggests that islet autoimmunity also targets neoepitopes expressed by the target cells, which may not be available for negative thymic selection. Differential expression of IA-2 and IGRP mRNAs in thymus and pancreas (157, 158) may promote autoimmunity, as the immune system may not be tolerant to alternatively spliced variants expressed in pancreas but not thymus (159). Many autoantigens in autoimmune disease are post-translationally modified (PTM) (160). Inflammation and stress are likely factors in the generation of PTM antigens, which derive from both normal and abnormal processes in cells. Predisposing HLA types are critical for the presentation of these epitopes to T cells (161, 162). Below, the major neoepitope classes associated with T1D are described.. Neoepitopes generated by PTM. A PTM epitope exists in the insulin A chain (A1-A13): T cell recognition requires oxidized cysteine residues at A6 and A7, with the formation of a vicinal disulfide bond between them (60). ...
Market Insights. According to American Autoimmune Related Diseases Association (AARDA), autoimmune diseases are caused by functional turbulence caused to immune system. Autoimmune reactions occur when the immune system produces autoantibodies that attack and destroy healthy tissues in the body rather than infectious agents. These autoantibodies cause inflammation, pain, and organ damage. Autoimmune disease is one of the top 10 leading causes of death in girls and women in all age groups up to 64 years of age. A close genetic relationship exists among autoimmune disease, explaining clustering in individuals and families as well as a common pathway of disease. The currently available treatment comprises chemical-based drugs such as immunosuppressant, corticosteroids and NSAIDs. Biological drugs are considered as the most developing segment of autoimmune diseases treatment market due to target-specific activity, less side-effects and high patient compliance compared to chemical- based drugs. The ...
Islet-associated protein-2 (IA-2) and IA-2β (also known as phogrin) are unique neuroendocrine-specific protein tyrosine phosphatases (PTPs). The IA-2 family of PTPs was originally identified from insulinoma cells and discovered to be major autoantigens in type 1 diabetes. Despite its expression in the neural and canonical endocrine tissues, data on expression ...
SSB antibody [3H9] (Sjogren syndrome antigen B (autoantigen La)) for ICC/IF, IHC-P, IP, WB. Anti-SSB mAb (GTX83560) is tested in Human, Dog samples. 100% Ab-Assurance.
Lindop, R., et al. Long-term Ro60 humoral autoimmunity in primary Sjögrens syndrome is maintained by rapid clonal turnover. Clinical Immunology. 0, 148(1). 01/07/2013.. ...
Clonal deletion of autoreactive T cells in the thymus is not the sole mechanism for the induction of tolerance to self-antigens since partial depletion of peripheral CD4(+) T cells from neonatal and adult animals results in the development of organ-specific autoimmunity. Reconstitution of these immu …
Dr. Bellot responded: Immunosuppression. Since the condition is produced by an abnormal immune response, the treatment is to reduce production of the |a href="/topics/antibody" track_data="{
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Synonyms for autoantibody in Free Thesaurus. Antonyms for autoantibody. 2 words related to autoantibody: rheumatoid factor, antibody. What are synonyms for autoantibody?
The human immune system is designed to detect and protect the body from invading microbes and viruses. Large families of pattern recognition receptors identify RNA in the circulation, a hallmark of viral infection, and respond with a robust, pleiotropic activation of cytokines. The activation of the recognition receptors mobilizes the immune system to eliminate the invading virus. Many patients with lupus and Sjögrens have circulating RNA-containing autoantigens, which mimic the initial steps of viral infection and lead to the production of autoantibodies. ...
Autoantigens[edit]. An autoantigen is usually a normal protein or protein complex (and sometimes DNA or RNA) that is recognized ...
tTG: tissue transglutaminase (auto antigen of Celiac disease). *TMEPAI: encoding protein Transmembrane prostate androgen- ...
2011). "Investigations of Caspr2, an autoantigen of encephalitis and neuromyotonia". Ann. Neurol. 69: 303-311. van Sonderen, A ...
"Entrez Gene: AMPH amphiphysin (Stiff-Man syndrome with breast cancer 128kDa autoantigen)".. ... the dominant autoantigen of paraneoplastic stiff-man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14". Human ... "The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer". The ... "Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer". Molecular Medicine. 4 ...
Autoantigens}-, Dobavljeno iz "https://sh.wikipedia.org/w/index.php?title=Topoizomeraza&oldid=2383016" ...
Th1 overactivation against autoantigens will cause Type 4 delayed-type hypersensitivity. Tuberculin reaction or Type 1 diabetes ... Th2 overactivation against autoantigen will cause Type1 IgE-mediated allergy and hypersensitivity. Allergic rhinitis, atopic ... Overactivation of THαβ against autoantigen will cause type 2 antibody-dependent cytotoxic hypersensitivity. Myasthenia gravis ...
Le Romancer M, Reyl-Desmars F, Cherifi Y, Pigeon C, Bottari S, Meyer O, Lewin MJ (1994). "The 86-kDa subunit of autoantigen Ku ... Ku80 has been referred to by several names including: Lupus Ku autoantigen protein p80 ATP-dependent DNA helicase 2 subunit 2 X ... Cao QP, Pitt S, Leszyk J, Baril EF (1994). "DNA-dependent ATPase from HeLa cells is related to human Ku autoantigen". ... Myung K, He DM, Lee SE, Hendrickson EA (1997). "KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen ...
Teuscher C, Wild GC, Tung KS (1982). "Immunochemical analysis of guinea pig sperm autoantigens". Biol reprod. 26 (2): 218-229. ...
... can generate autoantigens by cleaving in disordered regions and linker regions of antigens exposing new epitopes and ... Darrah E (2010). "Granzyme B cleavage of autoantigens in autoimmunity". Cell Death and Differentiation. 17 (4): 624-32. doi: ...
Individual autoantigens are deposited in an array of dots onto a surface such as polystyrene. A single array could consist of ... Autoantigens present on the blebs of apoptotic cells are also prone to modification, which can increase their immunogenicity. ... Similar to the flow cytometry method of ANA detection, the MIA uses wells containing autoantigens and HEp-2 extract coated ... Blebs on apoptotic cells contain nearly all the autoantigens found in SLE, and phagocytes bind these apoptotic cells and ...
1991). "Wegener's autoantigen and leukemia". Blood. 77 (6): 1398-9. PMID 2001463. Rao NV, Wehner NG, Marshall BC, et al. (1991 ... Labbaye C, Musette P, Cayre YE (1991). "Wegener autoantigen and myeloblastin are encoded by a single mRNA". Proc. Natl. Acad. ... 1990). "Wegener's autoantigen decoded". Nature. 346 (6284): 520. doi:10.1038/346520a0. PMID 2377228. Wilde CG, Snable JL, ... van der Geld YM, Limburg PC, Kallenberg CG (February 2001). "Proteinase 3, Wegener's autoantigen: from gene to antigen". J. ...
RoSSA interacts with autoantigens in patients with Sjögren's syndrome and systemic lupus erythematosus. TRIM21 can be used to ... The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes". J. Clin. Invest. 87 (1): 177-186. doi:10.1172/JCI114968. ... Frank MB, McCubbin VR, Heldermon C (1995). "Expression and DNA binding of the human 52 kDa Ro/SSA autoantigen". Biochem. J. 305 ... Keech CL, Gordon TP, McCluskey J (1996). "Structural differences between the human and mouse 52-kD Ro autoantigens associated ...
"Identification of tyrosine hydroxylase as an autoantigen in autoimmune polyendocrine syndrome type I". Biochemical and ... Tyrosine hydroxylase is also an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I.[44] ...
"Increased noncanonical splicing of autoantigen transcripts provides the structural basis for expression of untolerized ...
Knowledge of binding epitopes on the autoantigen is necessary to understand the subsequent pathologic events. Predicted 3D ...
Dohlam, JG; Lupas, A; Carson, M (1993). "Long charge-rich alpha-helices in systemic autoantigens". Biochem Biophys Res Commun. ... A physicochemical analysis of common structural motifs present in 109 human autoantigens revealed that tropomyosins have the ... highest number of such motifs, and thus a very high propensity to act as autoantigens. In addition to the role tropomyosins ...
Blaes F, Fühlhuber V, Preissner KT (2007). "Identification of autoantigens in pediatric opsoclonus-myoclonus syndrome". Expert ...
1993). "Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen ... "Entrez Gene: ICA1 islet cell autoantigen 1, 69kDa". Nepom GT (1996). "Glutamic acid decarboxylase and other autoantigens in ... Islet cell autoantigen 1 is a protein that in humans is encoded by the ICA1 gene. This gene encodes a protein with an arfaptin ... 1998). "Anti-BSA antibodies do not cross-react with the 69-kDa islet cell autoantigen ICA69". J. Autoimmun. 11 (3): 223-31. doi ...
Solute carrier family 25 (mitochondrial carrier; Graves disease autoantigen), member 16 is a protein in humans that is encoded ...
tTG is treated as an autoantigen, especially in people with certain HLA-DQ2 and HLA-DQ8 alleles and other gene variants that ... The main autoantigen of dermatitis herpetiformis is epidermal transglutaminase (eTG), a cytosolic enzyme involved in cell ... Immunological studies revealed findings that are similar to those of coeliac disease in terms of autoantigens. ...
"The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes". Proc. Natl. Acad. Sci. U.S.A ...
... is related to tTG and is the autoantigen of DH. It appears that all DH patients have or are susceptible on wheat ingestion to ... In PBC anti-mitochondrial antibodies are directed toward 3 mitochondrial autoantigens (pyruvate dehydrogenase, oxoglutarate ...
"Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase ...
2005). "Identification of specific autoantigens in Sjögren's syndrome by SEREX". Immunology. 116 (1): 53-63. doi:10.1111/j.1365 ...
Winqvist O, Karlsson FA, Kämpe O (June 1992). "21-Hydroxylase, a major autoantigen in idiopathic Addison's disease". The Lancet ...
Activated islets may express autoantigens that have only limited expression in quiescent islets. The often times striking ... disparity in HLA-DR/DQ associations with disease may involve differences in the immunological recognition of autoantigens. ... interesting observation that may have potential pathogenic implications is the observation that of all islet cell autoantigens ... predictability and disease intervention studies have been enhanced through the identification of the islet cell autoantigens in ...
Primary and metastatic carcinomas are epithelial in origin and comprise by far the largest group of malignant tumors in humans. In most of these tumors, T and Tn antigens, whose epitopes have been synthesized, are uncovered and immunoreactive. In all other tissues T and Tn antigens are masked and not accessible to the immune system; they are generally precursors in normal complex carbohydrate chains. Thus, carcinomas have antigens recognized as foreign by the patients immune system. The expression of T and Tn antigens has pathogenic and clinical consequences, and the antigens themselves are powerful histological markers in carcinoma diagnosis and frequently in prognosis. Most patients distinguish their carcinoma from all other cells, as shown by strong autoimmune responses to T antigen. These responses are readily measured by assays, and they allow detection of carcinomas with greater sensitivity and specificity frequently earlier than previously possible. Moreover, the extent of T and Tn ...
Autoantigen discovery with a synthetic human peptidome.. Larman HB1, Zhao Z, Laserson U, Li MZ, Ciccia A, Gakidis MA, Church GM ... However, current approaches to characterize autoantigens have, in most cases, met only with limited success. Here we present a ... Immune responses targeting self-proteins (autoantigens) can lead to a variety of autoimmune diseases. Identification of these ... Application of a synthetic human proteome to autoantigen discovery through PhIP-Seq ...
... Hui Liu, Rong Fu, Yihao Wang, ... Vinitha Ganesan, Dana P. Ascherman, and Jonathan S. Minden, "Immunoproteomics technologies in the discovery of autoantigens in ...
Nucleosomes are major T and B cell autoantigens in systemic lupus erythematosus.. Bruns A1, Bläss S, Hausdorf G, Burmester GR, ... T cell responses to autoantigens, including DNA, have been reported only incidentally in SLE patients. Nevertheless, in murine ... We present evidence that nucleosomes are major autoantigens in human SLE and that antinucleosomal antibodies are highly ...
... indicating that this specific CNS autoantigen, or some of its determinants, can induce a pathogenic response across animal ... clearly indicates that MOG is probably an important target autoantigen in this disease. ... Myelin oligodendrocyte glycoprotein Multiple sclerosis Experimental autoimmune encephalomyelitis Demyelination Autoantigen ...
... a putative autoantigen for type 1 diabetes). This review will focus specifically on insulin as a primary autoantigen, an ... The autoantigens of Type 1A diabetes may be divided into subgroups based on their tissue distributions: Beta-cell-specific ... Insulin as a Primary Autoantigen for Type 1A Diabetes. J. M. Jasinski1,2 and G. S. Eisenbarth2,3 ... We are pursuing the hypothesis that insulin is a primary autoantigen for type 1 diabetes, and thus the pathogenesis of the ...
Nature Reviews Nephrology, Published online: 13 June 2019; doi:10.1038/s41581-019-0168-xIn a collaborative effort, researchers have identified unusual protein deposits of exostosin 1 and exostosin 2 in patients with PLA2R and THSD7A-negative membranous nephropathy, many of whom had systemic lupus erythematosus, lupus nephritis or other forms of autoimmunity. Although serum exostosin antibodies wer...
Immunomodulation of RA Patients PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens. Smadar Gertel,1,2 ... PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens," Mediators of Inflammation, vol. 2017, Article ID ...
We identified a novel bovine antigen and homologous human autoantigen and designated it as UACA (uveal autoantigen with coiled ... Identification of a novel autoantigen UACA in patients with panuveitis.. Yamada K1, Senju S, Nakatsura T, Murata Y, Ishihara M ... To identify the target autoantigens in Vogt-Koyanagi-Harada disease, we made use of an immunoscreening of a bovine uveal cDNA ...
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination.. Berer K1, Mues M, Koutrolos M, ... of autoantibody-producing B cells from the endogenous immune repertoire depends on availability of the target autoantigen, ...
Autoantibodies and their corresponding autoantigens are intensively studied to provide clues to the understanding of disease ...
A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease ... copri, the greater the autoantibody responses against these autoantigens.. Figure 3. Autoantibody correlations with P. copri ... Both autoantigens are highly expressed in inflamed synovial tissue; they share homologous T cell epitopes with Prevotella and ... A highly expressed human protein, apolipoprotein B-100, serves as an autoantigen in a subgroup of patients with Lyme disease. J ...
Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered. Nonsequestered MCGA (NS-MGCA) egressed from normal tubules, as evidenced by their ability to interact with systemically injected antibodies and form localized immune complexes outside the Sertoli cell barrier. NS-MGCA derived from cell fragments that were discarded by spermatids during spermiation. They egressed as cargo in residual bodies and maintained Treg-dependent physiological tolerance. In contrast, sequestered MGCA (S-MGCA) were undetectable in residual bodies and ...
Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance. Kenneth S.K. Tung,1,2,3 Jessica Harakal,2,3 ... It also does not apply to the S-MGCA targeted in EAO after vasectomy (32). The selection of pathogenic autoantigens in a given ... Systemic tolerance is autoantigen dependent and involves multiple mechanisms (5). Tolerance begins in the thymus, controlled ... and autoantigen recognition (13) that occurs in the regional lymph nodes. Each regional lymph node expresses unique TCR ...
A tale of two autoantigens. Add to your list(s) Download to your calendar using vCal ... University of Cambridge , Talks.cam , Immunology and Medicine Seminars , A tale of two autoantigens ...
Pathogenic models of RA nowadays include smoking as a relevant trigger factor of immune reactions to autoantigens modified by ... Bang H, Egerer K, Gauliard A (2007) Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid ... As an ubiquitous expressed auto-antigen, vimentin might be of special relevance in triggering ACPA production. Vimentin ... Although reactivity against modified vimentin was predominant, the modified peptides were also recognized as autoantigens by ...
Emerging roles for the Ro 60-kDa autoantigen in noncoding RNA metabolism.. Sim S1, Wolin SL. ... Emerging roles for the Ro 60 kDa autoantigen in noncoding RNA metabolism ... Emerging roles for the Ro 60 kDa autoantigen in noncoding RNA metabolism ... Emerging roles for the Ro 60 kDa autoantigen in noncoding RNA metabolism ...
Heat inactivation of Ku autoantigen: possible role in hyperthermic radiosensitization.. Burgman P1, Ouyang H, Peterson S, Chen ... shown a constitutive DNA-binding factor in rodent cells that is inactivated by heat shock to be identical to Ku autoantigen. Ku ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
... *Download PDF Copy ... The discovery of DNAJB9 as a putative autoantigen in FGN paves the way for the development of new diagnostic and therapeutic ... Therefore, DNAJB9 may be an autoantigen, or a normal protein that is the target of an autoimmune response. ...
Identification of tissue transglutaminase as the autoantigen of celiac disease.. Dieterich W1, Ehnis T, Bauer M, Donner P, ... However, the identification of the endomysial autoantigen(s) has remained elusive. We identified tissue transglutaminase as the ... Transglutaminase is identified as the autoantigen of celiac disease. [Nat Med. 1997] ... suggesting that this structure contains one or more target autoantigens that play a role in the pathogenesis of the disease. ...
In addition, the prevalence, characteristic autoantigens, and autoantibodies of minor autoimmune diseases associated with AD ... Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability ... autoantigens and their autoepitopes, genetics, animal models, associated autoimmune diseases, pathogenesis, natural history, ...
Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain.. Marchalonis JJ1, Kaymaz H, Dedeoglu ... that humans naturally produce against human T-cell receptor beta chains and to localize the recognized peptide autoantigens in ...
Alpha B-crystallin · Autoimmunity · Microbial infection · Multiple sclerosis · T cells · Autoantigen · Crystallin · Myelin · ... Health · Tolerance · Autoantigen · Crystallin · Myelin · Myelin associated glycoprotein · Allergic encephalomyelitis · Animal ... The myelin-associated protein, αB-crystallin, is considered a candidate autoantigen in multiple sclerosis (MS). In the present ... Copyright (C) 2000 Elsevier Science B.V. Chemicals/CAS: Autoantigens; Crystallins; Immunodominant Epitopes; Peptide Fragments; ...
  • Moreover, in the constitutive presence of their soluble antigen, some autoreactive clones are able to acquire a germinal center phenotype, to induce Aicda gene expression and to introduce somatic mutations in the IgG heavy chain variable region on amino acids forming direct contacts with the autoantigen. (garvan.org.au)
  • PTPRN and PTPRN2 (this gene) are both found to be major autoantigens associated with insulin-dependent diabetes mellitus. (wikipedia.org)
  • This gene product is thought to be an autoantigen associated with rheumatoid arthritis. (wikipedia.org)
  • RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. (nih.gov)
  • 19:837-847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. (nih.gov)
  • We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. (pnas.org)
  • Alterations in this peptide epitope result in a potent antagonist that interferes with antigen-specific human T cell clones responding to this diabetes-associated autoantigen. (pnas.org)
  • The presented antigen identification strategy offers an opportunity for identifying up to now unknown neural autoantigens. (frontiersin.org)
  • Our data provide evidence that autoantigen as well as the CD40L expressed by activated nonneoplastic T cells may drive the evolution of low-grade MALT-type lymphomas either directly or by paracrine mechanisms and that antigen may contribute to lymphoma pathogenesis. (hindawi.com)
  • Thus, autoreactivity toward de novo-expressed β-cell autoantigens will not accelerate autoimmunity unless large number s of antigen-experienced autoreactive T-cells expressing the appropriate chemokine receptors are present. (diabetesjournals.org)
  • A role for active antigen selection of the citrulline-reactive synovial B cells was supported by the strong bias toward amino acid replacement mutations in ACPA + antibodies and by their loss of reactivity to citrullinated autoantigens when somatic mutations were reverted to the corresponding germline sequences. (rupress.org)
  • A homology search revealed a peptide from human leukocyte function-associated antigen-1 (hLFA-1) as a candidate autoantigen. (lymenet.org)
  • Identification of the initiating bacterial antigen and a cross-reactive autoantigen may provide a model for development of autoimmune disease. (lymenet.org)
  • The presence of antibody together with expression of antigen within the joint implicates citrullinated α-enolase as a candidate autoantigen that could drive the chronic inflammatory response in RA. (biomedcentral.com)
  • Single studies have also identified it as an autoantigen associated with severe asthma and a putative target antigen of anti-endothelial cell antibody in Behçet's disease. (wikipedia.org)
  • A view has therefore emerged that in the majority of individuals for the majority of life, destructive autoimmunity is held in check by populations of Tregs, recognizing autoantigens and responding through a variety of regulatory pathways ( 5 - 8 ). (diabetesjournals.org)
  • For the first time, we demonstrate in vivo that a noncross-reactive infectious agent can activate and induce autoreactive B cells to isotype switching and autoantigen-driven mutations, but on a nonautoimmune background, tolerance mechanisms prevent the formation of consequently dangerous autoimmunity. (garvan.org.au)
  • This thesis investigates the creation of ASIT for autoimmunity through the co-delivery of an immunomodulator and autoantigen. (ku.edu)
  • Overall, the results presented dissertation provide evidence for the successful creation of ASIT for autoimmunity by combining immunomodulator and autoantigen. (ku.edu)
  • Yalaka, Bharathi, "Cytoplasmic Proteins as Autoantigens in the Development of Inflammatory Heart Disease" (2017). (unl.edu)
  • To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20, 240 human proteins, for IgA-bound autoantigens since IgAs are a major immunoglobulin isotype in the lung. (mcponline.org)
  • Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays, and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. (mcponline.org)
  • Self-proteins (autoantigens) altered before or during tumor formation can elicit an immune response ( 13 - 19 ). (mcponline.org)
  • Unexpectedly, mechanical stretch also reduced the expression of TLR3 and of proteins known to represent autoantigens in inflammatory autoimmune myopathies (Mi-2, HRS, DNA-PKcs, U1-70). (sigmaaldrich.com)
  • Interestingly, stimulation or inhibition of calmodulin, NOS, HGF or c-Met molecules in vitro affected the expression of autoantigens and TLR3 proteins confirming their role in the inhibition of autoantigens and TLR3 during mechanical stretch. (sigmaaldrich.com)
  • Molecular characterization of two human autoantigens: unique cDNAs encoding 95- and 160-kD proteins of a putative family in the Golgi complex. (rupress.org)
  • We therefore analyzed B and T cell responses to autoantigens potentially involved in the pathogenesis of RA, including IgG, citrullinated proteins, stress proteins, glucose-6-phosphate isomerase, and heterogeneous nuclear ribonucleoprotein (hnRNP)-A2 (RA33). (jimmunol.org)
  • These data suggest that the E2 subunit of PDH is an autoantigen in halothane hepatitis and that molecular mimicry of CF 3 CO-proteins by the E2 subunit of PDH is due to the similar structures of CF 3 CO-Lys and lipoic acid. (springer.com)
  • In normal physiology, lymphocytes that recognise human proteins (autoantigens) either undergo programmed cell death (apoptosis) or become non-functional. (wikipedia.org)
  • Although immediate-Type I skin reactions to human dander have been described six decades ago, only the recent application of molecular biology to allergology research allowed fast and detailed characterization of IgE-binding autoantigens. (uzh.ch)
  • An autoimmune disease with multiple molecular targets abrogated by the transgenic expression of a single autoantigen in the thymus. (rupress.org)
  • This, together with our demonstration that there is a predominant T cell response to MOG in patients with multiple sclerosis, clearly indicates that MOG is probably an important target autoantigen in this disease. (springer.com)
  • The target autoantigen for the pathogenic CD4 + T cells has been defined as the H + /K + ATPase, the proton pump of the parietal cells located in the gastric mucosa ( 14 , 15 ). (jimmunol.org)
  • One interesting observation that may have potential pathogenic implications is the observation that of all islet cell autoantigens described, only two (i.e., 64 kD/GAD, 38 kD) are reactive in their native configurations, implying that recognition of conformational epitopes is most important. (jci.org)
  • By comparing the Ab responses to skin transglutaminases we could show that CD and DH are diseases where the main autoantigens are distinct but share common epitopes. (rupress.org)
  • Indeed, three of these candidate autoantigen epitopes, corresponding to residues 115-127, 274-286, and 554-566 of hGAD65, were immunogenic when used to immunize mice transgenic for HLA-DR4 ( 16 ). (pnas.org)
  • This suggests that some infiltrating CD4 positive T cells in BALF shared epitopes on autoantigens. (nii.ac.jp)
  • In addition, epitopes from other infectious agents, allergens and autoantigens are being curated. (wikipedia.org)
  • We have previously demonstrated that cell division autoantigen 1 (CDA1), which enhances transforming growth factor-β signaling, is upregulated in diabetes. (diabetesjournals.org)
  • We have previously shown that cell division autoantigen 1 (CDA1) is upregulated in diabetes and enhances TGF-β signaling, including in the vasculature ( 23 - 25 ). (diabetesjournals.org)
  • Its open reading frame of 2079 base pairs encodes a predicted polypeptide of 693 amino acids named CDA1 (cell division autoantigen-1). (garvan.org.au)
  • Cell division autoantigen 1 (CDA1) enhances TGF-β signaling in renal and vascular cells, and renal expression of CDA1 is elevated in animal models of diabetes. (asnjournals.org)
  • Our group has previously identified that the pathologic profibrotic effects of TGF-β in DN are, at least in part, mediated by enhanced TGF-β signaling modulated by cell division autoantigen 1 (CDA1). (asnjournals.org)
  • It is widely believed that nTregs are selected based on recognition of self-peptides, but it is not clear whether nTregs recognize organ-specific autoantigens, or whether they are activated by ubiquitous self-Ags and suppress organ-specific responses via bystander suppression. (jimmunol.org)
  • Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N -acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. (jci.org)
  • Recently, we have shown a constitutive DNA-binding factor in rodent cells that is inactivated by heat shock to be identical to Ku autoantigen. (nih.gov)
  • We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. (nih.gov)
  • Autoantigen candidates were identified from microarray expression profiling of human and rodent pancreas and islet cells and screened with radioimmunoprecipitation assays using new-onset T1D and prediabetic sera. (pnas.org)
  • We show that chronic infection by Borrelia burgdorferi of Tg animals expressing human rheumatoid factor (RF) B cells (of low or intermediate affinities) in the absence or in the constitutive presence of the autoantigen (represented here by chimeric IgG with human constant region) breaks their state of immunological ignorance, leading to the production of RFs. (jci.org)
  • RESEARCH DESIGN AND METHODS We isolated and cloned islet-specific IL-10-secreting CD4 + T-cells from nondiabetic individuals after brief ex vivo exposure to islet autoantigens using cytokine capture technology and examined their phenotype and regulatory potential. (diabetesjournals.org)
  • In recent years, we have developed approaches that allow the functional interrogation of human autoreactive T-cells directly ex vivo for their ability to respond to islet autoantigens ( 14 , 15 ). (diabetesjournals.org)
  • We show here that these autoantigens are clustered in two distinct populations of blebs at the surface of apoptotic cells. (rupress.org)
  • These autoantigen clusters have in common their proximity to the ER and nuclear membranes, sites of increased generation of reactive oxygen species in apoptotic cells. (rupress.org)
  • We have shown that recruitment of naive and in vitro-activated autoreactive CD8 + T cells into endogenous islets requires local autoantigen expression. (diabetesjournals.org)
  • Here, we demonstrate that absence of an autoantigen in syngeneic extrapancreatic islet grafts in diabetic hosts renders the grafts "invisible" to cognate memory (and naïve) T cells. (diabetesjournals.org)
  • A further confusing aspect of the story was that CD4 + T lymphocytes specific for HspB5 were found both in mice with experimental autoimmune encephalomyelitis (EAE) and MS patients, but unlike CD4 + T cells specific for myelin components, the HspB5-specific T cells did not induce EAE in mice ( 9 ), which is inconsistent with a definition of a disease-associated autoantigen. (jimmunol.org)
  • Pristane-induced arthritis (PIA) is driven by autoreactive T cells but no autoantigen has been identified to date. (jimmunol.org)
  • Significantly, we demonstrate that purified MZBs are able to present the autoantigen insulin to diabetogenic T-cells. (diabetesjournals.org)
  • In this study, we demonstrate that naive CD4 + Foxp3 − T cells specific for a naturally expressed autoantigen (H + /K + ATPase) can be converted to Foxp3 + T regulatory cells (Tregs) when stimulated in presence of TGFβ. (jimmunol.org)
  • Blebs on apoptotic cells contain nearly all the autoantigens found in SLE, and phagocytes bind these apoptotic cells and phagocytose them. (wikipedia.org)
  • Autoantigens present on the blebs of apoptotic cells are also prone to modification, which can increase their immunogenicity. (wikipedia.org)
  • 2012: Post-Aire maturation of thymic medullary epithelial cells involves selective expression of keratinocyte-specific autoantigens, Front. (wikipedia.org)
  • Furthermore, disparity in HLA-DR/DQ associations with disease may involve differences in the immunological recognition of autoantigens. (jci.org)
  • These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. (nih.gov)
  • ZnT8 was originally identified as an EST chosen from a list of 68 candidate islet autoantigens that was compiled from multidimensional analyses of microarray mRNA expression profiling experiments. (pnas.org)
  • The discovery of DNAJB9 as a putative autoantigen in FGN paves the way for the development of new diagnostic and therapeutic tools to help care for patients with this disease,' said Kelly Smith, MD PhD, senior author of the University of Washington study. (news-medical.net)
  • The discovery of TGc as the main endomysial autoantigen failed to explain why only a proportion of gluten sensitive patients show symptoms of DH and whether there is a difference in the antigenic repertoire between CD and DH. (rupress.org)