Cutting Edge Issues in Polymyositis

Skeletal muscle is the target tissue of immunoflogistic processes in patients affected with idiopathic inflammatory myopathies (IIM). IIM are classified into three major forms: polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. Recent data suggest that, in the major subsets of myositis, antigens in muscles drive a B-cell antigen-specific immune response. Moreover, some non-immunological mechanisms have been advocated. In this regard, an increased expression of Jo-1 and Mi-2 in muscle biopsies from PM and DM patients compared to normal muscle has been demonstrated; these candidate autoantigens in myositis are expressed at high levels in regenerating muscle cells rather than in mature myotubes. Myositis autoantigen upregulation has also been observed in neoplastic tissues, thus representing a potential link between cancer and autoimmunity in myositis. Myositis-specific autoantibodies (MSA) are disease markers and target intracellular proteins involved in key processes such as translocation and nuclear transcription. Myositis target antigens encompass aminoacyl-tRNA synthetases, the Mi-2 helicase/histone deacetylase protein complex, the signal recognition particle ribonucleoprotein, together with novel target antigens including p155/140, CADM-140, and SAE. Despite their high specificity for autoimmune myositis, MSA target non-muscle restricted proteins ubiquitary to all cell types, making the specific muscle involvement difficult to explain. Non-immunological mechanisms also seem to contribute to the pathogenesis of IIM; activation of endoplasmic reticulum stress response due to muscle regeneration and inflammation but independent to MHC-1 up-regulation has been recently reported in patients with myositis.