Antimitochondrial antibodies in rheumatic diseases: beyond primary biliary cholangitis

Antimitochondrial antibodies (AMAs) targeting the E2 subunit of the pyruvate dehydrogenase complex are the serological hallmark of primary biliary cholangitis (PBC), but may also occur across systemic autoimmune rheumatic diseases. This narrative review integrates clinical and experimental evidence on AMAs in rheumatic diseases, delineating disease-specific patterns and clinical implications beyond the hepatobiliary context. AMAs and other mitochondrial autoantibodies have been reported in systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren disease, and inflammatory myopathies. In systemic sclerosis and Sjögren disease, AMAs frequently indicate autoimmune overlap with PBC. In lupus and rheumatoid arthritis, mitochondrial autoantibodies have been associated with systemic inflammation, apoptosis, and innate immune activation. In inflammatory myopathies, AMAs identify a distinct phenotype characterized by chronic muscle involvement and increased cardiac risk. Thus, mitochondrial autoimmunity extends beyond hepatobiliary disease, and its interpretation should consider disease context, potentially indicating polyautoimmunity, systemic immune activation, or distinct clinical phenotypes.