HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis

Objective. Patients with polymyositis/dermatomyositis (PM/DM) who express anti-melanoma differentiation associated protein 5 (anti-MDA5) antibodies frequently present with interstitial lung disease (ILD). The aim of this study was to investigate the association of HLA-DRB1 with anti-MDA5 expression in PM/DM. Methods. The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population. Results. Frequencies of DRB1*04: 01 [17.0% vs 1.3%, corrected p value (p(c)) = 3.8 x 10(-8), OR 16.2, 95% CI 6.6-39.7] and *12: 02 (42.6% vs 19.3%, p(c) = 0.008, OR 3.1, 95% CI 1.7-5.7) were significantly higher in anti-MDA5-positive patients with PM/DM compared with the controls. The frequencies of DRB1*04: 01 (p = 5.2 x 10(-6), OR 17.1, 95% CI 5.3-54.9) and *12: 02 (p = 3.8 x 10(-4), OR 3.1, 95% CI 1.7-5.7) in anti-MDA5-positive patients with DM-ILD were higher than in the controls, whereas the frequencies of DRB1*04: 01 and *12: 02 did not differ between the anti-MDA5-negative patients with DM-ILD and controls. No difference in the frequency of DRB1 alleles, other than *04:01, carrying the "shared epitope" (SE), i.e., *01: 01, *01: 02, *04: 05, and *10: 01, was observed between the controls and patients with DM stratified by the presence of anti-MDA5 and ILD. Conclusion. DRB1*04: 01 and *12: 02 confer susceptibility to anti-MDA5 antibody production in DM, which cannot be explained by the SE hypothesis.