Peptide cargo tunes a network of correlated motions in human leucocyte antigens.
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ABSTRACT:
SUBMITTER: Hopkins JR
PROVIDER: S-EPMC8651013 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry.MethodsNine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10?000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted.ResultsIn both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR)?=?2.069, 95% asymptotic CIs (CI(95)) 1.486, 2.881; P?<?0.001] and in Spanish patients (OR?=?6.707, CI(95) 3.974, 11.319; P?<?0.001) as well as in anti-topo-positive patients: Italy (OR?=?2.642, CI(95) 1.78, 3.924; P?<?0.001) and Spain (OR?=?20.625, CI(95) 11.536, 36.876; P?<?0.001). In both the populations we also identified an additional risk allele (HLA-DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR?=?1.724, CI(95) 1.482, 2.005; P?<?0.001) or topo I antibodies (OR?=?0.5, CI(95) 0.384, 0.651; P?<?0.001).ConclusionsWe describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc.
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