Subtle differences in HLA DQ haplotype-associated presentation of AChR α-chain peptides may suffice to mediate myasthenia gravis

PR Deitiker, M Oshima, RG Smith, DR Mosier… - …, 2006 - Taylor & Francis
PR Deitiker, M Oshima, RG Smith, DR Mosier, MZ Atassi
Autoimmunity, 2006Taylor & Francis
The HLA DQA1 and DQB1 alleles were determined on a set of 24 myasthenia gravis
patients that had previously been examined for their T-cell proliferative responses to the 18
overlapping peptides representing the extracellular domain of h AChR α-chain. Patient
responses according to assumed cis or trans haplotypes were significantly higher in most
cases relative to normal controls. Comparisons of in vitro peptide-stimulated T-cell
responses of patient pairs which had DQA1: DQB1 in common displayed responses in …
The HLA DQA1 and DQB1 alleles were determined on a set of 24 myasthenia gravis patients that had previously been examined for their T-cell proliferative responses to the 18 overlapping peptides representing the extracellular domain of hAChR α-chain. Patient responses according to assumed cis or trans haplotypes were significantly higher in most cases relative to normal controls. Comparisons of in vitro peptide-stimulated T-cell responses of patient pairs which had DQA1:DQB1 in common displayed responses in tighter distribution relative to comparisons in which patient pairs did not share the same DQA1:DQB1 haplotype. Similar haplotypes, such as DQA1*0102:DQB1*0602 and DQA1*0102:DQB1*0604, tended to exhibit similar responses and were grouped according to this similarity. Modified F-test and Student's T-test analyses on DQ isoform bearing groups revealed that high responses to peptide α34–49 were associated with A1*0102:B1*0602/0604, A1*0301:B1*0302 and A1*0401/0303:B1*0301. Peptide α146–162 showed higher responses in A1*0301:B1*0302 group and moderate responses in A1*0401/0303:B1*0301 groups. Differences in the age of disease onset relative to DQ haplotypes were also observed. Groups of A1*0301:B1*0302, A1*0501:B1*0201 and A1*0102:B1*0604 showed earlier ages of disease onset relative to those of A1*0102:B1*0602 or A1*0505:B1*0301.
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