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Comparative HLA Alleles and Haplotypes of Bone Marrow Volunteers Recruiting in the Asian and European Parts of Russia.

HLA typing of 9126 haematopoietic stem cell donors living in the Asian and European parts of Russia and identifying themselves as Russians was performed using NGS technology in 2-field resolution at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. The study of donors in the Asian part of Russia disclosed 77 alleles at the HLA-A locus, 111 at the HLA-B locus, 58 at the HLA-C locus, 54 at the HLA-DRB1 locus, and 26 at the HLA-DQB1 locus. Donors of the European part of Russia are characterised by the following allelic diversity: 87 alleles at the HLA-A locus, 136 at the HLA-B locus, 72 at the HLA-C locus, 67 at the HLA-DRB1 locus, and 37 at the HLA-DQB1 locus. The most common five-locus haplotype in both populations is HLA-A*01:01 ~ HLA-C*07:01 ~ HLA-B*08:01 ~ HLA-DRB1*03:01 ~ HLA-DQB1*02:01. Throughout the study, 26 new alleles were revealed.

Humans

Distinct HLA Associations for Antibody Multireactivity With Citrulline-Containing Type II Collagen Epitopes Versus More Limited Antibody Reactivity With Citrulline-Containing IgG Epitopes in Rheumatoid Arthritis.

OBJECTIVE: Anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) can be promiscuous, with cross-reactive binding to many antigens containing short motifs, or private with little cross-reactivity. Also, ACPA reactivity patterns differ among patients with RA, including for motif-containing epitopes in important self-antigens like collagen and IgG (bound by RA-associated rheumatoid factors [RFs]), with limited understanding of the underlying mechanism. The objective of this study was to determine if HLA alleles associate with ACPA reactivity patterns. METHODS: For 100 ACPA+RF+ participants with RA, serum IgG binding was quantified by enzyme-linked immunosorbent assay to 10 citrulline-containing peptides derived from Type II collagen and IgG1 (nine with motifs), and HLA loci were genotyped. Also, antibody and serum multireactivity were evaluated. HLA alleles present differentially in RA participants with high versus low IgG binding to specific peptides, as well as with multireactivity versus limited reactivity were identified by Fisher's exact test. RESULTS: Serum IgG multireactivity for citrulline-glycine motif-containing collagen peptides was high, at least partially due to promiscuous antibodies. HLA-DQA1*01:02 was present in more participants with anticitrullinated collagen antibodies and multireactive sera. In contrast, serum multireactivity was low for IgG1-derived peptides due at least in part to more private antibodies. Shared epitope-containing HLA-DRB1*04:01 was present more frequently in participants with RA-associated RFs irrespective of the citrulline-serine motif and less frequently in participants with anticitrullinated collagen antibodies. Several HLA alleles associated with specific antibody reactivities. CONCLUSION: Different HLA alleles may contribute to the different reactivity patterns of promiscuous anticitrullinated collagen antibodies and more private RA-associated RFs.

Humans

Host Genetic Factors and Clinical Comorbidities Associated With Tuberculosis Risk.

HLA influence the immune response, shaping genetic susceptibility or resistance to tuberculosis (TB). This study aimed to investigate the associations of host genetics and comorbidities with TB infection in Taiwanese populations. This retrospective case-control study utilised data from the Taiwan Precision Medicine Initiative. TB cases and non-TB controls were compared using genome-wide association studies (GWAS), HLA allele typing, and genotype data. Multivariate logistic regression identified independent predictors of TB and interactions between risk factors. A total of 390 TB cases and 3,909 controls were analysed. Risk factors for TB included bronchiectasis (OR&#x2009;=&#x2009;2.76; 95% CI 1.54-4.44; p&#x2009;<&#x2009;0.001), diabetes mellitus (OR&#x2009;=&#x2009;1.30; 95% CI 1.00-1.68; p&#x2009;=&#x2009;0.050), malignancy (OR&#x2009;=&#x2009;1.46; 95% CI 1.15-1.85; p&#x2009;=&#x2009;0.002), smoking (OR&#x2009;=&#x2009;1.42; 95% CI 1.08-1.88; p&#x2009;=&#x2009;0.012), and steroid use (OR&#x2009;=&#x2009;1.66; 95% CI 1.29-2.13; p&#x2009;<&#x2009;0.001). HLA-DRB1*16:02 was associated with a higher frequency in the TB group (OR&#x2009;=&#x2009;1.47; 95% CI 1.04-2.09; p&#x2009;=&#x2009;0.030). Interaction analysis showed HLA-DRB1*16:02 increased TB risk in non-smokers (OR&#x2009;=&#x2009;1.58; 95% CI 1.02-2.46; p&#x2009;=&#x2009;0.042), but not in smokers. HLA-DRB1*16:02 was associated with a higher risk for TB. While carriers of HLA-DRB1*16:02 did not exhibit an increased risk of TB among smokers, we demonstrated a heightened risk among non-smokers.

Humans