Distribution of anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses in MDA5+ dermatomyositis

Abstract

The anti-melanoma differentiation-associated gene 5 (MDA5) antibody is the main predictor of interstitial lung disease (ILD) in DM and clinically amyopathic DM (CADM). Nevertheless, a subset of MDA5+ patients have a favourable prognosis. We aimed to determine the possibility of using anti-MDA5 antibody isotypes and IgG subclasses for evaluating ILD risk. The isotypes (IgG, IgA and IgM) of anti-MDA5 were detected in serum samples of 36 anti-MDA5+ patients with DM/CADM using ELISA. IgG subclasses of anti-MDA5 antibodies were further investigated. Laboratory findings and cumulative survival were analysed based on the isotypes of anti-MDA5 and subclasses of anti-MDA5 IgG. Among the MDA5+ patients with DM/CADM, the positive rates of anti-MDA5 IgG, IgA and IgM were 100, 97 and 6%, respectively. The positive rates of anti-MDA5 IgG1, IgG2, IgG3 and IgG4 were 72, 25, 0 and 28%, respectively. The incidence of acute interstitial pneumonia, mortality rate and serum ferritin were significantly higher in anti-MDA5 IgG1+ patients than in anti-MDA5 IgG1- patients with DM/CADM (P = 0.0027, 0.015, 0.0011, respectively). The sensitivity and specificity of anti-MDA5 IgG1 for predicting mortality were 100 and 41.7%, respectively. A combination of anti-MDA5 IgG1 and IgG4 for predicting mortality yielded better specificity (87.5%). IgA and IgG are the primary anti-MDA5 antibody isotypes. Anti-MDA5 IgG1 is the primary component of MDA5 IgG subclasses and anti-MDA5 IgG1 and IgG4 might serve as useful biomarkers for predicting mortality in DM-ILD.