Loading...


  • DQA1
  • There is only one common cis-isoform of DQ8 because the linked DQA1*03 alleles(2) occur over the majority of the population, DQ8.1 is the overwhelming majority cis-isoform of DQ8. (wikipedia.org)
  • Autoimmunity
  • To test this hypothesis we analyzed the role of HLA class I and class II gene polymorphisms in the progression from diabetes-associated autoimmunity to clinical disease. (diabetesjournals.org)
  • CONCLUSIONS These results confirm that class I alleles affect the progression of diabetes-associated autoimmunity and demonstrate interactions between class I and class II alleles. (diabetesjournals.org)
  • This form of diabetes is strongly inherited, but lacks immunological evidence for β cell autoimmunity and it is not human leukocyte antigen associated. (mysteria.cz)
  • The hypothesis underlying the DAISY data in this study is that DPB1 allele frequency differences may at least partially account for the higher rate of autoimmunity and type 1 diabetes observed in high-risk, first-degree relatives compared with high-risk individuals without a first-degree relative (see below). (diabetesjournals.org)
  • We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. (readbyqxmd.com)
  • In defining mechanisms, it is necessary to consider that type 1 diabetes has a preclinical period in which there is autoimmunity against pancreatic β-cell antigens ( 3 ). (diabetesjournals.org)
  • genotype
  • When children with the DR3/DR4 genotype were separately analyzed, HLA-B*39 had a strong effect (OR 6.6, P = 0.004 and OR 7.5, P = 0.007, after the appearance of the first and the second autoantibody, respectively). (diabetesjournals.org)
  • Patients with type 2 diabetes and healthy subjects carrying the T allele or the TT genotype at the rs7903146 locus exhibit impaired insulin secretion and defects in glucagon suppression, particularly in response to incretins and oral glucose, as well as abnormal insulin processing ( 17 - 19 ). (diabetesjournals.org)
  • peptide
  • TSHR peptide epitopes bound to HLA-class II are presented by antigen-presenting cells (APCs) to CD4+ T cells (Figure 2 ). (frontiersin.org)
  • T cell recognition was dependent on the formation of a vicinal disulfide bond between adjacent cysteine residues at A6 and A7, which did not alter binding of the peptide to HLA DR4. (rupress.org)
  • Insulin
  • The clones recognized a naturally processed, HLA DR4-restricted epitope within the first 13 amino acids of the A-chain (A1-13) of human insulin. (rupress.org)
  • Recently, it was reported that HLA DR4-restricted, CD4 + T cells that react to the first 15 amino acids of the insulin A-chain make up a large proportion of T cells from the pancreatic lymph nodes of two subjects with who had T1D, but not from three healthy donors ( 15 ). (rupress.org)
  • HLA-DR and -DQ gene polymorphism in Latvian patients with insulin-dependent diabetes mellitus. (ld.ru)
  • molecule
  • Interaction by the complex of TSHR epitope, HLA-class II molecule, and T-cell receptor (TCR) is modified through binding of CD40 ligand to CD40 and of CTLA-4 to B7 ( 3 - 6 ). (frontiersin.org)
  • Two distinctly HLA-associated contiguous linear epitopes uniquely expressed within the islet antigen 2 molecule are major autoantibody epitopes of the diabetes-specific tyrosine phosphatase-like protein autoantigens. (ld.ru)
  • dendritic cells
  • The autoimmune response against beta-cells appears to begin in the pancreatic lymph node where T cells, which have escaped negative selection in the thymus, first meet beta-cell antigens presented by dendritic cells. (soc-bdr.org)
  • chromosome
  • The major histocompatibility complex (MHC), located on the short arm of Chromosome 6, is one of the most extensively studied regions in the human genome because of the contribution of multiple variants at this locus in autoimmune, infectious, and inflammatory diseases and in transplantation. (plos.org)
  • frequency
  • The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world. (wikipedia.org)
  • The MHC was first associated with disease in 1967 when HLA-B antigens were found at increased frequency in patients with Hodgkin's lymphoma . (plos.org)
  • diabetes
  • Several alleles of HLA-DQB1 are associated with an increased risk of developing type 1 diabetes. (wikipedia.org)
  • The locus also has the genetic name IDDM1 as it is the highest genetic risk for type 1 diabetes. (wikipedia.org)
  • OBJECTIVE Class II alleles define the main HLA effect on type 1 diabetes, but there is an independent effect of certain class I alleles. (diabetesjournals.org)
  • As predisposing genetic factors such as HLA alleles are known, immunological interventions to prevent type 1 diabetes are of great interest. (mysteria.cz)
  • Genetic associations between type 1 diabetes and alleles at the HLA class II locus DPB1 have been previously reported. (diabetesjournals.org)
  • Genetic associations of DPB1 alleles with type 1 diabetes susceptibility have been reported ( 5 , 7 - 12 ), with one report showing no detectable association ( 13 ). (diabetesjournals.org)
  • These data demonstrate reproducibility of associations among ethnic groups and support a role for the DPB1 locus as a risk factor for type 1 diabetes. (diabetesjournals.org)
  • The transcription factor 7 like 2 ( TCF7L2 ) locus contains the single nucleotide polymorphism (SNP) most strongly associated with type 2 diabetes risk, with an ∼30% increase per risk allele ( 3 ). (diabetesjournals.org)
  • In a U.S. cohort, heterozygous and homozygous carriers of the at-risk alleles comprised 40.6% and 7.9%, respectively, of the control subjects and 44.3% and 18.3%, respectively, of the individuals with type 2 diabetes ( 3 ). (diabetesjournals.org)
  • The locus has no known association with type 1 diabetes overall ( 4 - 8 ), with conflicting reports in latent autoimmune diabetes in adults ( 8 - 16 ). (diabetesjournals.org)
  • For disease diagnosis and confirmation, there is no known association of DQB1*0305 with either coeliac or autoimmune diabetes. (wikipedia.org)
  • HLA polymorphism in type 1 diabetes Tunisians. (ld.ru)
  • GAD65 antibody prevalence and association with thyroid antibodies, HLA-DR in Chinese children with type 1 diabetes mellitus. (ld.ru)
  • pathogenesis
  • To date, linear or conformational epitopes of TSHR-ECD, as well as the molecular structure of the epitope-binding groove in HLA-DR, were reported to be related to the pathogenesis in GD. (frontiersin.org)
  • Thus the results of this study provide basis for a correlation between the MHC class I locus and the role of IELs in CD pathogenesis. (biomedcentral.com)
  • Human
  • Major histocompatibility complex, class II, DQ beta 1, also known as HLA-DQB1, is a human gene and also denotes the genetic locus that contains this gene. (wikipedia.org)
  • As a result, they strongly bind to human leucocyte antigens (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. (readbyqxmd.com)
  • The major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. (plos.org)
  • Shortly afterward, Jean Dausset recognized the human MHC, or human leukocyte antigen (HLA) region, so named because Dausset originally demonstrated MHC antigens on the surface of white blood cells . (plos.org)
  • Inheritance
  • Dominant inheritance of a milder APS1 phenotype has been described recently due to heterozygous AIRE gene mutations that inactivate the normal allele (dominant negative mutations). (springer.com)
  • epitopes
  • We review and update the role of immunogenic TSHR epitopes and HLA in GD, and offer perspectives on TSHR epitope specific treatments. (frontiersin.org)
  • Murine
  • Murine models of GD and HLA-transgenic mice have played a pivotal role in elucidating the immunological mechanisms. (frontiersin.org)
  • Historically, the murine MHC locus, H2 , was identified and subsequently named for its role in histocompatibility almost 60 years ago by George Snell . (plos.org)
  • DQ2.5
  • 8.3 of 11.1% of the A33-B58 in the Baloch Pakistani can is linked to DR3 and presumbably DQ2.5 (There are few exceptions outside of Africa). (wikipedia.org)
  • immune cells
  • Genetically predisposed individuals could be influenced by an environmental trigger (i.e., dietary iodine, infection, pregnancy, cytokine therapy) that induces an autoimmune response against thyroid-specific antigens by infiltrating immune cells. (springer.com)
  • Disease
  • One measure of whether the association of an allele with a disease reflects a true effect of the locus or is simply due to LD is the observation of that association in multiple ethnic groups. (diabetesjournals.org)
  • partially
  • The risk is partially shared with the HLA-DR locus (DR3 and DR4 serotypes). (wikipedia.org)
  • DQ8 is determined by the antibody recognition of β8 and is complicated by the fact that DQ8 recognizes some HLA-DQB1*03 encoded isoforms well, partially or not well at all (See serology) DQ β3.2 and β3.5 are best recognized as DQ8. (wikipedia.org)
  • autoantibody
  • Multivariate analysis demonstrated a significant protective effect of the A*03 allele (odds ratio [OR] 0.61, P = 0.042 after the first and OR 0.55, P = 0.027 after the second autoantibody), whereas the B*39 allele had a promoting effect after seroconversion for the second autoantibody (OR 2.4, P = 0.014). (diabetesjournals.org)
  • risk
  • Certain HLA-DQB1 alleles are also linked to a modest increased risk of multiple sclerosis. (wikipedia.org)
  • 1 ) Puerto Rican case and control subjects, 2 ) Mexican-American simplex families, and 3 ) high-risk (DR3/DR4) individuals with and without an affected relative. (diabetesjournals.org)
  • In the hepatocyte, TCF7L2 risk alleles are associated with gain of function and increased hepatic glucose release during fasting ( 17 ). (diabetesjournals.org)
  • DQ8 increases the risk for rheumatoid arthritis and is linked to the primary risk locus for RA, HLA-DR4. (wikipedia.org)
  • Although false reaction with DQB1*0302 is low, the efficiency of the positive reaction is not good and there is a risk of false detection of DQB1*0305 which could create incompatibility. (wikipedia.org)
  • Haplotype
  • These GRC haplotype contigs, called 'alternate loci', are constructed so that they begin with additional anchor sequence derived from the reference. (ucl.ac.uk)
  • There are many other gene-alleles within the haplotype, including more than 250 coding loci that produce transcripts. (wikipedia.org)
  • At 4.7 million nucleotides in length and ~300 genes the locus had resisted the effects of recombination, either as a consequence of recombination-obstruction within the DNA, as a consequence of repeated selection for the entire haplotype, or both. (wikipedia.org)
  • The haplotype begins before the TRIM27 locus approximately 28.8 million nucleotides from the telomere of chromosome 6's shorter arm. (wikipedia.org)
  • High affinity presentation of an autoantigenic peptide in type I diabetes by an HLA class II protein encoded in a haplotype protecting from disease. (ld.ru)
  • It is commonly found in linkage disequilibration within the A*3301-Cw*0802-B*1402 haplotype which can be extended to DRB1 and DQB1 in certain instances(See Below). (wikipedia.org)
  • One haplotype stands out, the A33-B58-DR3-DQ2 haplotype which is found in West Africa, in Sudan, and Pakistan, scattered along West Indias coast, the Turkic republics and appears to have recently introgressed into Korea (post-Yayoi period of Japan) and China. (wikipedia.org)
  • DQB1*0202 The second haplotype, like A33-B58 is found in Korea but not in Japan. (wikipedia.org)
  • affording genetic susceptibility
  • While human leukocyte antigen typing, autoantibody measurement, and thecharacterization of many regions affording genetic susceptibility have contributedtremendously to our ability to predict the onset of, comprehend the etiologyof, and track the progression of type 1 diabetes, these approaches are far fromcomplete in terms of their understanding. (ufl.edu)
  • peptide
  • We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. (diabetesjournals.org)
  • TSHR peptide epitopes bound to HLA-class II are presented by antigen-presenting cells (APCs) to CD4+ T cells (Figure 2 ). (frontiersin.org)
  • T cell recognition was dependent on the formation of a vicinal disulfide bond between adjacent cysteine residues at A6 and A7, which did not alter binding of the peptide to HLA DR4. (rupress.org)
  • An individual's HLA variants influence peptide binding and signal transduction after T cell receptor (TCR) engagement. (jci.org)
  • islet
  • HLA-DR binding analysis of peptides from islet antigens in IDDM. (ld.ru)
  • Two distinctly HLA-associated contiguous linear epitopes uniquely expressed within the islet antigen 2 molecule are major autoantibody epitopes of the diabetes-specific tyrosine phosphatase-like protein autoantigens. (ld.ru)
  • Type 1 diabetes is characterized by the presence of antibodies to a 65 kD Glutamic Acid Decarboxylase antigen (GAD), Insulinoma-associated protein-2 antibodies (IA-2 orICA512), which is now known as protein- tyrosine phosphatase (PTP), insulin autoantibodies (IAAs), and islet cell autoantibodies (ICAs), in blood that identify the autoimmune process that leads to β cell destruction. (mysteria.cz)
  • Autoantibodies against β-cell-specific antigens, such as proinsulin and insulin, GAD65, islet antigen-2, and zinc transporter 8, can usually be detected in serum before the clinical onset of the disease, but although the number of circulating autoantibodies is predictive for the development of T1D ( 1 ), predicting the onset of clinical disease remains a challenge. (diabetesjournals.org)
  • genotype
  • Patients with type 2 diabetes and healthy subjects carrying the T allele or the TT genotype at the rs7903146 locus exhibit impaired insulin secretion and defects in glucagon suppression, particularly in response to incretins and oral glucose, as well as abnormal insulin processing ( 17 - 19 ). (diabetesjournals.org)
  • However, genotype at thers2069762 locus did not directly associate with disease state. (ufl.edu)
  • insulin
  • HLA-DR and -DQ gene polymorphism in Latvian patients with insulin-dependent diabetes mellitus. (ld.ru)
  • The clones recognized a naturally processed, HLA DR4-restricted epitope within the first 13 amino acids of the A-chain (A1-13) of human insulin. (rupress.org)
  • CD4 + T cell clones that recognized this epitope were isolated from an HLA DR4 + child with autoantibodies to insulin, and therefore, at risk for T1D, but not from two healthy HLA DR4 + donors. (rupress.org)
  • Recently, it was reported that HLA DR4-restricted, CD4 + T cells that react to the first 15 amino acids of the insulin A-chain make up a large proportion of T cells from the pancreatic lymph nodes of two subjects with who had T1D, but not from three healthy donors ( 15 ). (rupress.org)
  • phenotype
  • Dominant inheritance of a milder APS1 phenotype has been described recently due to heterozygous AIRE gene mutations that inactivate the normal allele (dominant negative mutations). (springer.com)
  • autoantibody
  • Individuals with high risk human leukocyte antigen, autoantibody, andgenotypic profiles still escape overt disease, while in contrast individualswith low risk factors can progress to type 1 diabetes. (ufl.edu)
  • epitopes
  • To date, linear or conformational epitopes of TSHR-ECD, as well as the molecular structure of the epitope-binding groove in HLA-DR, were reported to be related to the pathogenesis in GD. (frontiersin.org)
  • We review and update the role of immunogenic TSHR epitopes and HLA in GD, and offer perspectives on TSHR epitope specific treatments. (frontiersin.org)
  • TSHR epitopes bound to HLA-class II presented on the surface of APC are the most crucial factor to determine immunogenicity. (frontiersin.org)
  • There is increasing evidence, mainly from animal models, that pathogenic T cells in autoimmune disease recognize epitopes that are formed by posttranslational modification of self-antigens ( 16 ). (rupress.org)
  • molecule
  • Interaction by the complex of TSHR epitope, HLA-class II molecule, and T-cell receptor (TCR) is modified through binding of CD40 ligand to CD40 and of CTLA-4 to B7 ( 3 - 6 ). (frontiersin.org)
  • DPB1
  • Genetic associations between type 1 diabetes and alleles at the HLA class II locus DPB1 have been previously reported. (diabetesjournals.org)
  • Genetic associations of DPB1 alleles with type 1 diabetes susceptibility have been reported ( 5 , 7 - 12 ), with one report showing no detectable association ( 13 ). (diabetesjournals.org)
  • The hypothesis underlying the DAISY data in this study is that DPB1 allele frequency differences may at least partially account for the higher rate of autoimmunity and type 1 diabetes observed in high-risk, first-degree relatives compared with high-risk individuals without a first-degree relative (see below). (diabetesjournals.org)
  • These data demonstrate reproducibility of associations among ethnic groups and support a role for the DPB1 locus as a risk factor for type 1 diabetes. (diabetesjournals.org)
  • proinsulin
  • Proinsulin is the major product of β cells and, with the possible exception of rare self-antigen-expressing cells in lymphoid tissues ( 5 ), is the only known T1D autoantigen that is expressed exclusively in β cells. (rupress.org)
  • the long class III VNTR allele is associated with higher levels of proinsulin mRNA in the thymus and decreased susceptibility to T1D ( 8 , 9 ). (rupress.org)
  • lymphoid tissues
  • Studies of organ donors with T1D that have examined T cells in pancreas, the diabetogenic insulitis lesion, and lymphoid tissues have revealed a broad repertoire of target antigens and T cell receptor (TCR) usage, with initial evidence of public TCR sequences that are shared by individuals with T1D. (jci.org)
  • homozygous
  • In a U.S. cohort, heterozygous and homozygous carriers of the at-risk alleles comprised 40.6% and 7.9%, respectively, of the control subjects and 44.3% and 18.3%, respectively, of the individuals with type 2 diabetes ( 3 ). (diabetesjournals.org)
  • diabetes
  • The locus has no known association with type 1 diabetes overall ( 4 - 8 ), with conflicting reports in latent autoimmune diabetes in adults ( 8 - 16 ). (diabetesjournals.org)
  • Although ∼70% of subjects with type 1 diabetes carry defined risk-associated genotypes at the HLA locus, only 3-7% of the carriers of such genetic risk markers develop the disease ( 5 ). (rupress.org)
  • After informed parental consent, HLA alleles associated with type 1 diabetes risk or protection were analyzed from cord blood, and subjects carrying risk-associated genotypes were followed over time to establish the time point of seroconversion and diabetes development. (rupress.org)
  • HLA-DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica. (ld.ru)
  • HLA polymorphism in type 1 diabetes Tunisians. (ld.ru)
  • GAD65 antibody prevalence and association with thyroid antibodies, HLA-DR in Chinese children with type 1 diabetes mellitus. (ld.ru)
  • In defining mechanisms, it is necessary to consider that type 1 diabetes has a preclinical period in which there is autoimmunity against pancreatic β-cell antigens ( 3 ). (diabetesjournals.org)
  • As predisposing genetic factors such as HLA alleles are known, immunological interventions to prevent type 1 diabetes are of great interest. (mysteria.cz)
  • This form of diabetes is strongly inherited, but lacks immunological evidence for β cell autoimmunity and it is not human leukocyte antigen associated. (mysteria.cz)
  • For disease diagnosis and confirmation, there is no known association of DQB1*0305 with either coeliac or autoimmune diabetes. (wikipedia.org)
  • Several alleles of HLA-DQB1 are associated with an increased risk of developing type 1 diabetes. (wikipedia.org)
  • The locus also has the genetic name IDDM1 as it is the highest genetic risk for type 1 diabetes. (wikipedia.org)
  • DQ2.5
  • 8.3 of 11.1% of the A33-B58 in the Baloch Pakistani can is linked to DR3 and presumbably DQ2.5 (There are few exceptions outside of Africa). (wikipedia.org)
  • partially
  • DQ8 is determined by the antibody recognition of β8 and is complicated by the fact that DQ8 recognizes some HLA-DQB1*03 encoded isoforms well, partially or not well at all (See serology) DQ β3.2 and β3.5 are best recognized as DQ8. (wikipedia.org)
  • The risk is partially shared with the HLA-DR locus (DR3 and DR4 serotypes). (wikipedia.org)
  • populations
  • DQB1*0305 gene product reacts slightly more intensely with DQ8 than DQ7 its generally rare in Europe and North America, except in a few indigeonous populations. (wikipedia.org)
  • high risk
  • 1 ) Puerto Rican case and control subjects, 2 ) Mexican-American simplex families, and 3 ) high-risk (DR3/DR4) individuals with and without an affected relative. (diabetesjournals.org)
  • Disease
  • One measure of whether the association of an allele with a disease reflects a true effect of the locus or is simply due to LD is the observation of that association in multiple ethnic groups. (diabetesjournals.org)
  • risk
  • In the hepatocyte, TCF7L2 risk alleles are associated with gain of function and increased hepatic glucose release during fasting ( 17 ). (diabetesjournals.org)
  • The lipid changes were not attributable to HLA-associated genetic risk. (rupress.org)
  • Although false reaction with DQB1*0302 is low, the efficiency of the positive reaction is not good and there is a risk of false detection of DQB1*0305 which could create incompatibility. (wikipedia.org)
  • Certain HLA-DQB1 alleles are also linked to a modest increased risk of multiple sclerosis. (wikipedia.org)