Clinical meaning
Antisynthetase syndrome is a systemic autoimmune condition defined by autoantibodies against aminoacyl-tRNA synthetases, most commonly anti-Jo-1 (anti-histidyl-tRNA synthetase). These enzymes catalyze amino acid attachment to tRNA during protein synthesis. When the immune system targets them, autoreactive CD8+ T cells and inflammatory cytokines attack multiple organs. The classic triad comprises inflammatory myopathy (proximal muscle inflammation with perimysial CD4+ T-cell infiltration), interstitial lung disease (ILD, most often nonspecific interstitial pneumonia or organizing pneumonia patterns driven by alveolar inflammation and fibrosis), and non-erosive polyarthritis. Environmental triggers such as respiratory viral infections may expose intracellular tRNA synthetases to the immune system in genetically susceptible individuals with HLA-DRB1*0301, initiating the autoimmune cascade. ILD is the primary determinant of morbidity and mortality, with progressive pulmonary fibrosis occurring if treatment is delayed.