Clinical features, pathogenesis, and treatment of anti-MDA5 antibody-positive interstitial lung disease

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis is one of the idiopathic inflammatory myopathies, which are connective tissue diseases characterized by inflammation of skeletal muscle and skin. It may be initiated by environmental and viral triggers, with genetic susceptibility contributing to type I interferon-mediated immune activation involving monocytes and macrophages that promote lung injury. These immune abnormalities result in characteristic cutaneous manifestations, vasculopathy, and a high prevalence of rapidly progressive interstitial lung disease. The presence of rapidly progressive interstitial lung disease is associated with a poor prognosis, and numerous studies have examined clinical factors and biomarkers related to disease progression and mortality, highlighting the need for more refined prognostic stratification and biomarker discovery. In recent years, improved outcomes have been reported in Japan with triple combination therapy, and therapeutic approaches targeting the type I interferon pathway have also been described. However, some patients remain refractory to treatment or experience disease relapse, highlighting persistent unmet clinical needs. This review summarizes the current knowledge regarding the etiology and clinical characteristics of anti-MDA5 antibody-positive dermatomyositis, describes biomarkers that are useful for assessment of disease activity and pathophysiology, and provides an overview of current therapeutic strategies.