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

J Rheumatol. 2023 Sep;50(9):1159-1164. doi: 10.3899/jrheum.2022-1321. Epub 2023 Jun 15.

Abstract

Objective: 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.

Methods: 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.

Results: 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-A*02:07, B*46:01, DRB1*04:07, DRB1*07:01, DRB1*08:03, DQB1*06:01, and DPB1*02:02-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-B*48:01, B*52:01, C*12:02, DRB1*04:05, DRB1*15:02, DPB1*05:01, and DPB1*09:01-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 DRB1*04:07 (odds ratio [OR 28.9]; corrected P = 2.7 × 10-6) and DQB1*06:01 (OR 4.0; corrected P = 1.6 × 10-4) alleles were significantly more prevalent in patients with anti-Mi-2 antibody than in controls.

Conclusion: This study demonstrates DM-specific autoantibodies defined immunogenetic subsets of DM.

Keywords: autoantibodies; autoimmune diseases; dermatomyositis; myositis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Autoantibodies
  • Dermatomyositis* / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-DQ beta-Chains / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Male
  • Retrospective Studies

Substances

  • HLA-DRB1 Chains
  • Autoantibodies
  • HLA-DQ beta-Chains