HLA‐D Region genes associated with autoantibody responses to histidyl‐transfer RNA synthetase (Jo‐1) and other translation‐related factors in myositis

Abstract

Myositis has been associated with HLA‐B8 and DR3, especially in white patients with polymyositis and serum anti‐Jo‐1 antibodies. Twenty‐eight patients with myositis and serum translation‐related autoantibodies anti‐Jo‐1, anti‐PL‐7, anti‐PL‐12, anti‐KJ, and anti‐SRP were studied for HLA class II specificities by Southern blotting with HLA‐DRβ, DQβ, and DQα probes. The association of HLA‐DR3 (DRw17) with anti‐Jo‐1 antibodies in white myositis patients was confirmed (P = 0.003, relative risk 8.9). However, HLA‐DRw52 haplotypes, regardless of subtype, were present in all of the white and black patients with serum anti‐Jo‐1 and other translation‐related autoantibodies. Moreover, one anti‐Jo‐1 positive patient had HLA‐DRw8, an HLA‐DRw52 haplotype on which the DRβ3 gene has been partially deleted. No HLA‐DQ specificity or allele was common to all patients. The HLA‐DR3, DR5, DRw6, and DRw8 haplotypes, which bear the HLA‐DRw52 specificity, share the most homology in the DRβ1 first hypervariable region at amino acid positions 9–13. Thus, this DRβ1 region appears to be the most likely candidate “epitope” for translation‐related autoimmune responses in inflammatory myositis.