Insights into pathogenesis and clinical implications in myositis-associated interstitial lung diseases

Purpose of review Interstitial lung diseases (ILDs) have been reported to be associated with myositis (including polymyositis and dermatomyositis). These myositis-associated ILDs carry significant morbidity and mortality. This review summarizes recent findings on myositis-associated ILD with a focus on pathogenesis and emerging treatment. Recent findings Recent advances in genetics have revealed 22 myositis-associated genome-wide loci, which were significantly enriched in regulatory regions in immune cells. An analysis of such disease-associated loci elucidated potential drug targets (e.g.,TYK2targeted by tofacitinib). In another study, an intronic variant inWDFY4in association with clinically amyopathic dermatomyositis (CADM) had an effect for higher expression of a truncatedWDFY4isoform. TruncatedWDFY4markedly enhanced the MDA5-mediated NF-kappa B activation and cell apoptosis, indicating the dysregulated WDFY4-MDA5 pathway as a novel pathogenesis of CADM. As a novel strategy, tofacitinib treatment showed a promising improvement in survival and clinical features of CADM-associated ILD. The genetic differences in the myositis-susceptible loci may explain the heterogeneous phenotypes and treatment responses in myositis-associated ILD. The understanding of pathogenesis with the genetic background as well as autoantibodies will enable the practice of personalized treatment in the management of the disease.