The complication of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) is associated with anti–aminoacyl–transfer RNA synthetase (anti-aaRS) antibody or anti–melanoma differentiation–associated gene 5 (anti–MDA-5) antibody positivity. Anti–MDA-5 antibody is associated with clinically amyopathic DM and fatal outcome due to rapidly progressive ILD in Asian populations. The association between genetic factors and anti–MDA-5 antibody–positive DM is unclear. This study was undertaken to investigate the HLA–DRB1 genotype in patients with anti–MDA-5 antibody–positive DM.
We examined genetic differences among 17 patients with anti–MDA-5 antibody–positive DM, 33 patients with anti-aaRS antibody–positive PM/DM, 33 patients with PM/DM without anti-aaRS antibody or ILD, and 265 healthy controls.
The frequencies of HLA–DRB1*0101 and DRB1*0405 were 29% and 71%, respectively, in patients with anti–MDA-5 antibody–positive DM, which were higher than the frequencies in healthy controls (10% and 25%, respectively). Among the 17 patients with anti–MDA-5 antibody–positive DM, 16 (94%) harbored either the DRB1*0101 or DRB1*0405 allele. The combined frequency of the DRB1*0101 allele and the DRB1*0405 allele was significantly higher in patients with anti–MDA-5 antibody–positive DM than in patients with PM/DM without anti-aaRS antibody or ILD, with an odds ratio (OR) of 42.7 (95% confidence interval [95% CI] 4.9–370.2) (P = 1.1 × 10−5), or in patients with anti-aaRS antibody–positive PM/DM (OR 13.3 [95% CI 1.6–112.6], P = 4.5 × 10−3).
Our findings indicate that HLA–DRB1*0101/*0405 is associated with susceptibility to anti–MDA-5 antibody–positive DM in the Japanese population.