The Antisynthetase Syndrome: A Review

Anti-synthetase syndrome (ASyS) is a relatively new and distinct clinical entity within the group of idiopathic inflammatory myopathies (IIM) characterized by the presence of autoantibodies targeting aminoacyl-tRNA synthetase (ARS), a family of enzymes responsible for protein translation but now recognized to possess important extracellular immunomodulatory functions. Anti-Jo-1 remains the most prevalent and studied antibody, but there exist additional antibodies, including PL-7, PL-12, EJ, OJ, KS, Zo, and Ha. These antibodies define a clinically similar but heterogenic syndrome with a variable combination of inflammatory myopathy, interstitial lung disease (ILD), inflammatory arthritis, and Raynaud’s phenomenon. Only a minority of patients initially present with multiple symptoms, whereas isolated pulmonary, muscle, or articular manifestations frequently predominate. Interstitial lung disease remains the predominant cause of morbidity and mortality, but neuromuscular involvement is central to disease pathogenesis and patient disability. Current evidence supports a concept of pathogenesis in which genetically susceptible individuals develop aberrant innate and adaptive immune responses from tissue injury, leading to persistent inflammation and progressive fibrosis. Despite advances in understanding ASyS, the disease remains associated with significant morbidity and mortality, largely driven by ILD. This review summarizes current evidence regarding pathogenesis, genetic susceptibility, clinical manifestations, diagnostic evaluation, and evolving treatment strategies for ASyS.