HLA-DPB1*0501-associated opticospinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies.
(1/246)
In order to clarify the relationship between the clinical phenotype and the human leucocyte antigen (HLA) in multiple sclerosis in Asians, 93 Japanese patients with clinically definite multiple sclerosis underwent clinical MRI and HLA-DPB1 gene typing studies. According to a neurological examination, 29 patients were classified as opticospinal multiple sclerosis, 17 as spinal multiple sclerosis and 47 as Western type multiple sclerosis showing the involvement of multiple sites in the CNS including either the cerebrum, cerebellum or brainstem. The opticospinal multiple sclerosis showed a significantly higher age of onset, higher expanded disability status scale scores and higher CSF cell counts and protein content than the Western type multiple sclerosis. On brain and spinal cord MRI, the opticospinal multiple sclerosis showed a significantly lower number of brain lesions, but a higher frequency of gadolinium-enhancement of the optic nerve and a higher frequency of spinal cord atrophy than in Western type multiple sclerosis. The frequency of the HLA-DPB1*0501 allele was found to be significantly greater in opticospinal multiple sclerosis (93%) than in healthy controls (63%, corrected P value = 0.0091 and relative risk = 7.9), but not in Western type multiple sclerosis (66%) or spinal multiple sclerosis (82%). The marked differences in the clinical and MRI findings as well as in the immunogenetic backgrounds between the opticospinal multiple sclerosis and Western-type multiple sclerosis together suggest that HLA-DPB1*0501-associated opticospinal multiple sclerosis is a distinct subtype of multiple sclerosis. (+info)
Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis.
(2/246)
OBJECTIVE: When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers. RESEARCH DESIGN AND METHODS: This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia. RESULTS: The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups. CONCLUSIONS: Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises. (+info)
Slow evolutionary loss of the potential for interspecific hybridization in birds: a manifestation of slow regulatory evolution.
(3/246)
Birds have lost the potential for interspecific hybridization slowly. This inference emerges from protein comparisons made on 36 pairs of bird species capable of hybridization. Micro-complement fixation tests show that hybridizable pairs of bird species differ by an average of 12 units of albumin immunological distance and 25 units of transferrin immunological distance. As these proteins evolve at a known and rather steady rate, it is inferred that the average hybridization species pair diverged from a common ancestor about 22 million years ago. The corresponding period for frog species pairs capable of hybridization is about 21 million years, while for hybridizable placental mammals it is only 2 to 3 million years. Thus birds resemble frogs in having lost the potential for interspecific hybridization about 10 times as slowly as have mammals. Birds have also been evolving very slowly at the anatomical level, particularly within the last 25 million years, according to Simpson, Romer, and many other vertebrate zoologists. In this respect they resemble frogs and differ from placental mammals, which have been undergoing unusually rapid anatomical evolution. Chromosomal evolution is also thought to have proceeded very slowly in both birds and frogs, relative to mammals. The above observations are consistent with the hypothesis that evolutionary changes in regulatory systems, that is, changes in the patterns of gene expression, provide the basis for both anatomical evolution and the evolutionary loss of hybridization potential. (+info)
Ontology for immunogenetics: the IMGT-ONTOLOGY.
(4/246)
MOTIVATION: IMGT, the international ImMunoGeneTics database (http:@imgt.cines.fr:8104), created by M.-P. Lefranc, is an integrated database specializing in antigen receptors (immunoglobulins and T-cell receptors) and major histocompatibility complex (MHC) of all vertebrate species. IMGT accurate immunogenetics data are based on the standardization of the biological knowledge provided by the 'ImMunoGeneTics' IMGT-ONTOLOGY. The IMGT-ONTOLOGY describes the classification and specification of terms needed for immunogenetics and bioinformatics. IMGT-ONTOLOGY covers four main concepts: 'IDENTIFICATION', 'DESCRIPTION', 'CLASSIFICATION' and 'OBTENTION'. These concepts allow an extensive and standardized description and characterization of immunoglobulin and T-cell receptor data. The controlled vocabulary and the annotation rules are indispensable to ensure accuracy, consistency and coherence in IMGT. IMGT-ONTOLOGY allows scientists and clinicians to use, for the first time, identical terms with the same meaning in immunogenetics. It provides a semantic repository that will improve interoperability between specialist and generalist databases. (+info)
Immunogenetics: changing the face of immunodeficiency.
(5/246)
Tables 1 and 2 highlight the enormous advances that have been made in the definition of the molecular defects underlying primary immunodeficiencies in the past decade. The identification of SAP as the gene defective in XLP now completes the molecular bases of all the recognised X linked syndromes. Of the autosomally inherited syndromes, only the genes for DiGeorge syndrome, hyper-IgE, and perhaps most importantly, common variable immunodeficiency remain to be elucidated. The major clinical benefits of this information have primarily been in offering more accurate and rapid molecular diagnoses. The ability to make a molecular diagnosis also increases the options for earlier definitive treatments such as bone marrow transplantation and somatic gene therapy. Finally, as illustrated by the studies on the functions of WASP and the gamma c/JAK-3 pathway, identification of the gene defect is the first step to understanding the molecular pathogenesis of the immunological abnormalities. (+info)
Permanent hapten-specific tolerance in B lymphocytes.
(6/246)
Tolerance to the hapten TNP was induced in mice congenic with CBA but bearing the Ig-b allotype (Ig-b mice). To induce a high degree of tolerance it was necessary to give five injections of TNP-sulphonate followed by an immunogenic challenge (alum precipitate of TNP-BSA with pertussis adjuvant). Lymph node or spleen cells from these mice were transferred, with or without an equal number of non-tolerant CBA spleen cells, to irradiated CBA recipients and these were challenged with a different TNP-protein conjugate. Anti-TNP antibody bearing the Ig-b allotype was then assayed separately from total anti-TNP, as a measure of the contributions made by tolerant and non-tolerant B-cell populations respectively. Tolerant lymph node cell did not depress the response of normal cells, nor did the normal cells 'break' the tolerance of the Ig-b population even when the latter had been treated with anti-T-cell serum and complement. No response was obtained from tolerant lymph node cells when the recipients were challenged at different time up to 12 weeks after transfer. By this time the control non-tolerant lymph node cells had also lost the capacity to respond. It is concluded that: (1) effectively permanent tolerance, which is not maintained by afferent mechanisms, can be induced in lymph node B cells; (2) B-cell tolerance can be greatly enhanced by immunogenic challenge; (3) spleen may contain a distinct population of B cells which is less susceptible to tolerance; and (4) the life-span of virgin lymph node B cells is probably less than 12 weeks. (+info)
Interactions of Fc receptors with antibodies against Ia antigens and other cell surface components.
(7/246)
Two Fc receptor-dependent tests were investigated to study the question of a relationship between Fc receptors and known cell surface antigens, in particular I region-associated (Ia) antigens: (a) a rosette assay with antibody-coated erythrocytes (EA) as indicator cells and normal mouse lymphoid cells as source of rosette-forming cells, and (b) a cytotoxicity test with antibody-coated erythrocytes as target cells and normal mouse spleen cells as a source of cytotoxic cells (K cells). EA rosettes were specifically inhibited by antibodies reacting with Ia antigens. Various other antisera reacting with antigens on B lymphocytes, like anti-Ly 4.2 (raised in H-2 identical mice), rabbit antimouse B-cell serum, or rabbit antimouse immunoglobulin, also specifically inhibited the rosettes. No inhibition occurred in the presence of allogeneic or xenogeneic antisera reacting with T lymphocytes. K-cell cytotoxicity was specifically inhibited by each of the antisera (reacting with either B cells or T cells). F(ab')2 fragments of anti-Ia antibodies could still specifically inhibit EA rosettes but they could not inhibit K-cell cytotoxicity. Similar results were obtained with F(ab')2 fragments of anti-immunoglobulin antibodies. These results indicate that the mechanism of inhibition of Fc receptors in the two tests was different. In neither of the tests could we find any evidence for a unique association between the Fc receptors and Ia antigens. The Fc receptors on K cells did not seem to be associated at all with Ia antigens. (+info)
Genetic control of the immune response to poly(Glu52Lys33Tyr15) in neonatally thymectomized high and low responder rats.
(8/246)
The immune response to poly (Glu52Lys33Tyr15) is under polygenic control and linked to the major histocompatibility complex of the rat. Aggregation of this antigen with methylated bovine serum albumin (MeBSA) eliminates the expression of genetic control by increasing the response of low responders and decreasing that of high responders. Humoral and cellular aspects of the immune response to both unaggregated and aggregated poly (Glu52Lys33Tyr15) were investigated in neonatally thymectomized high-responder ACI and low-responder F344 rats. T cells are necessary for responses to unaggregated poly (Glu52Lys33Tyr15) since thymectomy significantly decreased numbers of antibody-forming cells and serum antibody levels, and delayed hypersensitivity responses and antigen-induced in vitro proliferation. However, thymectomy had no significant effect on these parameters of immune responsiveness in either ACI or F344 rats immunized with poly (Glu52Lys33Tyr15)/MeBSA. Aggregation also increased IgG production and delayed hypersensitivity and antibody affinity in low responders. (+info)