LAUSR

OBJECTIVES This study aimed to investigate the high-resolution computed tomography (HRCT) characteristics of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5 DM-ILD), and to clarify the underlying mechanisms of the clinical phenomenon. METHODS Clinical data and HRCT patterns were compared between anti-MDA5 DM-ILD (n = 32) and antisynthetase syndrome-associated ILD (ASS-ILD) (n = 29). RNA sequencing of whole blood samples from the two groups, and in vitro experiments using human embryonic lung fibroblasts (HELFs), were conducted to explore the potential mechanisms of the clinical findings. RESULTS The anti-MDA5 DM-ILD subset had a significantly higher incidence of rapidly progressive ILD (RPILD) than ASS-ILD (65.6% vs 37.9%; p = 0.031). The relative percentage of the lung fibrosis HRCT pattern was significantly lower in the anti-MDA5 DM-ILD group, especially the RPILD subgroup (p = 0.013 and 0.003, respectively). RNA sequencing detected the upregulation genes including interferon-induced helicase C domain 1 (encoding MDA5), and a trend toward downregulated expression of TGF-β signalling components in anti-MDA5 DM-ILD. In vitro culture of HELFs revealed that upregulated expression of MDA5 in HELFs was correlated with the downregulated expression of alpha smooth muscle actin, connective tissue growth factor, collagen I, and collagen III by suppressing the TGF-β signalling pathway. CONCLUSIONS Anti-MDA5 DM-ILD patients have significantly less lung fibrosis and elevated MDA5 expression. The upregulated expression of MDA5 has relations with the suppression of the pro-fibrotic function of fibroblasts via the TGF-β signalling pathway, which may partially explain the mechanism of the clinical phenomenon.