antiMDA5

Anti-MDA5 refers to autoantibodies directed against the melanoma differentiation-associated protein 5, a cytoplasmic RNA helicase involved in sensing viral RNA and activating innate immune responses. Anti-MDA5 antibodies are one of the myositis-specific autoantibodies and are most frequently found in dermatomyositis, particularly in clinically amyopathic dermatomyositis (CADM). The presence of anti-MDA5 often marks a distinct clinical subset characterized by prominent skin findings and a high risk of rapidly progressive interstitial lung disease (RP-ILD).

Clinical features commonly include dermatomyositis skin manifestations such as heliotrope rash and Gottron papules, sometimes with palm involvement, oral ulcers, and mechanic’s hands. Muscle weakness may be minimal or absent, especially in CADM, while interstitial lung disease can be severe and rapidly progressive, appearing early in the disease course. Serum ferritin can be markedly elevated and may reflect disease activity; other inflammatory markers may be raised.

Diagnosis relies on serology demonstrating anti-MDA5 antibodies, typically measured by immunoprecipitation or modern immunoassays such as ELISA or line blot. Serology is often performed as part of a myositis-specific autoantibody panel. Imaging with high-resolution CT typically shows interstitial lung disease, while pulmonary function testing may reveal reduced diffusion capacity. Muscle enzymes can be normal or only mildly elevated, and electrodiagnostic testing may show nonspecific myopathic changes.

Management emphasizes immunosuppression to control skin disease and, critically, lung involvement. Regimens commonly include high-dose corticosteroids combined with calcineurin inhibitors, with additional agents such as mycophenolate mofetil, cyclophosphamide, or intravenous immunoglobulin. In RP-ILD, aggressive combination therapy is often pursued; targeted therapies such as janus kinase inhibitors have been reported in case series. Prognosis is guarded, with RP-ILD being a major determinant of survival, and ferritin level and extent of lung disease serving as important prognostic indicators.