Association Between HLA Alleles and Autoantibodies in Dermatomyositis Defined by Sarcoplasmic Expression of Myxovirus Resistance Protein A.

Abstract

The diagnosis in the studies analyzing HLA of dermatomyositis (DM) was based on a combined clinical category of polymyositis/DM. This retrospective study investigated the associations of HLA with 5 DM-specific autoantibodies in Japanese patients diagnosed by muscle pathology. We diagnosed Japanese patients with DM based on sarcoplasmic expression of myxovirus resistance protein A. These patients underwent investigation for 5 DM-specific autoantibodies and HLA genotyping. Of 175 patients (83 males and 92 females; range 1-86 yrs; mean 46 yrs), 173 (98.9%) had 1 of the 5 autoantibodies. Seven alleles-<i>A*02:07, B*46:01, DRB1*04:07, DRB1*07:01, DRB1*08:03, DQB1*06:01</i>, and <i>DPB1*02:02</i>-were more frequently detected in the patients with DM than healthy controls, but these associations were not significant after multiple testing correction. Stratifying by DM-specific autoantibodies, we found the associations of 6 already known and 7 new alleles-<i>B*48:01, B*52:01, C*12:02, DRB1*04:05, DRB1*15:02, DPB1*05:01</i>, and <i>DPB1*09:01</i>-with subsets of DM. Moreover, significant associations of 5 alleles with antinucleosome remodeling deacetylase complex (Mi-2) remained after multiple testing correction. In particular, the <i>DRB1*04:07</i> (odds ratio [OR 28.9]; corrected <i>P</i> = 2.7 × 10^-6) and <i>DQB1*06:01</i> (OR 4.0; corrected <i>P</i> = 1.6 × 10^-4) alleles were significantly more prevalent in patients with anti-Mi-2 antibody than in controls. This study demonstrates DM-specific autoantibodies defined immunogenetic subsets of DM.