Association of human leucocyte antigen-DRB1 alleles and the development of anti-melanoma differenti-ation-associated gene 5 antibodies in patients with dermatomyositis

Abstract

Objective To investigate the association of human leucocyte antigen (HLA-DRB1) with anti-melanoma differentiation-associated gene 5 (MDA5) expression in polymyositis/dermatomyositis (PM/DM). Methods Seventy patients with PM, 104 patients with DM and 400 healthy controls were included. Genoty-ping of HLA-DRB1 was performed using the sequencing-based typing method. Levels of anti-MDA5 were measured by enzyme linked immunosorbent assay using recombinant MDA5 antigen. The frequencies of HLA-DRB1 alleles were compared between the patients and controls using a chi-square test or Fisher's exact test. Results Frequencies of DRB1*04:01 [17.0% vs 1.3%, corrected P-value (Pc)=3.8×10-8; odds ratio (OR)=16.2;95% confidence interval (CI) (6.6, 39.7)] and DRB1*12:02 [(42.6% vs 19.3%, Pc=0.008; OR=3.1; 95% CI(1.7, 5.7)] were significantly higher in anti-MDA5 positive PM/DM patients compared with the controls. The frequencies of DRB1*04:01 [P=5.2×10-6, OR=17.1, 95%CI: (5.3, 54.9) and *12:02 [P=3.8×10-4, OR=3.1, 95%CI(1.7,5.7)] in anti-MDA5 positive DM-interstitial lung disease (ILD) patients were higher than those in the controls, whereas the frequencies of DRB1*04:01 and *12:02 did not differ between the anti-MDA5 negative DM-ILD patients and the 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 DM patients 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. Key words: Polymyositis; Dermatomyositis; Lung disease, interstitial; Human leucocyte antigen; Anti-melanoma differentiation-associated gene 5 antibody