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

The anti-melanoma differentiation-associated gene 5 (MDA5) antibody is the main predictor of interstitial lung disease (ILD) in dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM). Nevertheless, a subset of MDA5+ patients have a favorable 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 enzyme-linked immunosorbent assay (ELISA). IgG subclasses of anti-MDA5 antibodies were further investigated. Laboratory findings and cumulative survival were analyzed 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, 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 those 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.

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Authors: Mengya Chen, Qian Zhao, Licheng Diao, Ke Xue, Yeping Ruan, Feng Xue, Jian Li, Ruofei Shi, Meng Pan, Jie Zheng, Hua Cao