Disease relevance of HLA-DRB1

• We have therefore investigated the effects of the HLA-DRB1 locus on asthma and its intermediate phenotypes in Aboriginal people from the Kimberly region of Australia who were suffering from endemic hookworm infection [1].
• Prevalence of HLA-DRB1 genotype and altered Fas/Fas ligand expression in adrenocortical carcinoma [2].
• Although a number of studies reported the association of HLA-DRB1 and Crohn's disease (CD), the actual alleles associated with CD are considerably variable among populations [3].
• Maternal - offspring HLA-DRB1 compatibility in multiple sclerosis [4].
• CONCLUSIONS: The findings of the present study suggest that susceptibility of advanced endometriosis is not associated with HLA-DRB1 alleles in a Korean population, which is apparently not the case in the Japanese population [5].
• The risk of mortality due to ischemic heart disease or cancer in RA is increased in patients carrying HLA-DRB1 genotypes with particular homozygous and compound heterozygous SE combinations [6].

Psychiatry related information on HLA-DRB1

• We investigated a Japanese narcolepsy family, in which a de novo chromosomal recombination occurred between the HLA-DRB1 and HLA-B genes in the proband [7].
• The distribution of HLA-DRB1 and -DQB1 alleles and presence or absence of DRB3/4/5 alleles were examined in 60 narcoleptic patients with clear-cut cataplexy, and the results were compared with two groups of healthy controls: 200 randomly selected controls and 144 DRB1*1501-DQB1*0602 positive controls [8].
• The allele frequency of the HLA-DRB1 gene was compared between groups of 48 clinically diagnosed elderly Alzheimer's disease (AD) cases and 44 pathologically confirmed elderly control cases [9].

High impact information on HLA-DRB1

• Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis [10].
• Survival was adversely affected by an interval from diagnosis to transplantation of one year or more, an HLA-DRB1 mismatch, a high body-weight index, and an age of more than 50 years [11].
• Maternal-fetal disparity in alleles of HLA- DRB1, DQA, and DQB occurred in 26 of 34 pregnancies characterized by remission or improvement (76 percent), as compared with 3 of 12 pregnancies characterized by active arthritis (25 percent) (odds ratio, 9.7; P = 0.003) [12].
• Evidence for linkage disequilibrium between HLA-DRB1 gene and multiple sclerosis. The French Research Group on Genetic Susceptibility to MS [13].
• The human immune system DRB1 genes are extremely polymorphic, with gene lineages that coalesce into an ancestor who lived around 60 million years ago, a time before the divergence of the apes from the Old World monkeys [14].

Chemical compound and disease context of HLA-DRB1

• TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers.RESULTS:At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients [15].
• The influence of glutamic acid (E)-alanine (A) dimorphism at position 74 of the DR4 beta chain on cytotoxic T cell recognition of an antigenic rubella virus peptide, E1(273-284), was studied using a panel of B cell lines and B cell transfectants expressing different HLA-DRB1 alleles as antigen-presenting cells and targets in 51Cr-release assays [16].
• Genetic variants at DRB1 (Dw subtypes), DQB, and C4 loci were compared in rheumatoid disease subjects with or without the extra-articular feature of Felty's syndrome or major vasculitis [17].
• More rapid myeloid engraftment was associated with marrow serologically matched at HLA-A and HLA-B, DRB1 match, higher cell dose (in non-T-cell-depleted cases), younger recipient, recipient seronegativity for cytomegalovirus (CMV), male donor, no methotrexate for graft-versus-host disease prophylaxis, and transplantation done in more recent years [18].
• METHODS: The distribution of HLA-DQB1 and DRB1, DRB3, DRB4, and DRB5 in 269 HCWs with latex allergy, 56 latex-sensitized patients with spina bifida (SB), and 90 nonatopic control subjects under special consideration for hevein-specific IgE was examined [19].

Biological context of HLA-DRB1

• The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing [20].
• Linkage analysis of rheumatoid arthritis in US and UK families reveals interactions between HLA-DRB1 and loci on chromosomes 6q and 16p [21].
• A region of high acetylation located in the intergenic sequences between HLA-DRB1 and HLA-DQA1 was discovered and termed XL9 [22].
• OBJECTIVE: We therefore analyzed the association between the phenotype of high IgE serum levels and six microsatellite markers on chromosomes 5q31 and 11q13, as well as HLA-DRB1, in a random sample of the adult East German population [23].
• HLA-DRB1 and DQB1 allele genotyping and autoimmune regulator (AIRE) polymorphisms located in exons 6, 8 and 10 were investigated by PCR-based methods [24].

Anatomical context of HLA-DRB1

• These data further confirm that HLA-DRB1 alleles are the major restriction molecules for MV-P and MV-N measles virus antigen presentation to T cells [25].
• Studies on the human leukocyte antigen-DR in patients with endometriosis: genotyping of HLA-DRB1 alleles [26].
• This new allele, officially named DRB1*1150, was detected while performing HLA-DRB1 high-resolution typing of a candidate for bone marrow transplantation [27].
• The errors were detected during development of sequencing based typing (SBT) methods for the HLA-DRB1 locus and were confirmed by sequencing cell lines from the 10th International Histocompatibility Workshop (IHW) [28].
• Lymphocyte proliferation in response to the peptide pool corresponding to amino acids 289-372 of HEV ORF2 protein was associated with presence of HLA-DRB1 allele 010X [29].

Associations of HLA-DRB1 with chemical compounds

• To elucidate the origin of these duplicated loci and allelic divergences at the most polymorphic DRB1 locus, introns 4 and 5 as well as the 3' untranslated region (altogether approximately 1,000 base pairs) of seven HLA-DRB loci, three HLA-DRB1 alleles, and nine nonhuman primate DRB genes were examined [30].
• The DRB1 gene is polymorphic at residue 86, encoding valine or glycine [31].
• Molecular cloning and sequencing confirmed that the new DRB1 allele is identical to DRB1*0101 at exon 2 except for a single nucleotide substitution at codon 37 (TauCC-->TauAlphaC), changing the encoded serine to tyrosine [32].
• The absence of aspartic acid (Asp) at position 57 of the DRB1 chain and the presence of arginine (Arg) at position 52 of the DQA1 chain correlated positively with both types of IDDM [33].
• Also, DRB1 alleles that are negatively associated with MS all encode a Gly at position 86, suggesting that the residue at position 86 may be critical in conferring susceptibility and protection to MS [34].

Enzymatic interactions of HLA-DRB1

• Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/split antigen level for HLA-A and -B [35].

Regulatory relationships of HLA-DRB1

• The highly polymorphic HLA-DRB1 locus is always expressed at a higher level than the HLA-DRB3 locus, and functional assays indicate that the proximal promoter of DRB1 is indeed more active than that of DRB3 [36].
• Analyses also suggested that shared epitope DRB1 genotype significantly influenced the occurrence of seropositive RA [37].
• We analyzed the genotype for HLA-DRB1 alleles by digestion of polymerase chain reaction-amplified genes with the restriction endonucleases (PCR-RFLP) method to investigate the influence of HLA-DR antigen "splits" at the DRB1 gene level on the incidence of acute graft rejection in the renal transplant [38].
• HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis [39].

Other interactions of HLA-DRB1

• RESULTS: DQ3 (DQBI*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles predisposed individuals to RA independently of SE-positive DRB1 alleles [40].
• Peptide-specific cytokine responses and HLA-DRB1 allele associations revealed that, for the MV-P peptide, the allele with the strongest association with both IFN-gamma (P = 0.02) and IL-4 (P = 0.03) secretion was DRB1*0301 [41].
• These results indicated that both of HLA-DRB1 and TNFA promoter polymorphisms contribute to the susceptibility to CD in an independent manner [3].
• The increase in DMB*0101 allele and homozygote genotype frequencies was independent of a linkage disequilibrium between DMB and DRB1 alleles [42].
• With allele-specific probes, 22 DRB1, 8 DQA1, 13 DQB1, and 12 DPB1 alleles were found in this panel [43].

Analytical, diagnostic and therapeutic context of HLA-DRB1

• CONCLUSIONS: HLA-DRB1 gene is the major genetic determinant in HLA class II region for children with type 1 AIH [24].
• In this report we describe a new HLA-DRB1 allele, DRB1*1353, which was initially recognized by a discrepancy between the results obtained with polymerase chain reaction using sequence-specific oligonucleotide (PCR-SSO) and sequence-specific primers (PCR-SSP) [44].
• To determine the correlation between HLA class II polymorphisms and these lymphomas, we applied DNA typing for HLA-DRB1 and HLA-DQB1 on 50 Dutch patients with testicular and 48 with nodal DLBCL and compared the frequencies with a cohort of healthy Dutch controls [45].
• A frequency of particular HLA-DRB1 alleles in patients was compared with that of a control group of 700 unrelated ethnically matched individuals as well as 193 age-matched women without endometriosis [46].
• Significant association between HLA-DRB1 and attention deficit hyperactivity disorder (ADHD) in a case-control study of 31 subjects has been reported but there have been no other published studies following up these results [47].

References