Association of human leucocyte antigen-DRB1 alleles and the development of anti-melanoma differentiation-associated gene 5 antibodies in patients with dermatomyositis / 中华风湿病学杂志

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.Genotyping of HLA-DRB1 was performed using the sequencing-based typing method.Levels of anti-MDA5 were measued 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.