Immune manifestations of inflammatory muscle disease

Evidence of autoimmune muscle injury and of systemic autoimmunity is seen in PM and DM. In typical PM, a cell-mediated attack on muscle fibers by CD8+ cytotoxic T cells predominates, directed at an unknown antigen. In DM, vascular injury is prominent, with loss of muscle capillaries and ischemic muscle damage, apparently mediated by local complement activation in small muscle vessels. Although humoral immunity seems more important in the pathogenesis of DM, serum autoantibodies are commonly found in both forms. About one third of patients have MSAs, whereas others have less specific antibodies such as anti-U1RNP, often associated with overlap syndromes involving myositis. MSAs are mutually exclusive and define characteristic clinical subgroups. Antibodies to five of the aminoacyl-tRNA synthetases are each associated with an "antisynthetase syndrome" marked by myositis, ILD, arthritis, and other features, but individual patients have only a single antisynthetase. Rare autoantibodies to certain translation factors may be associated with a similar syndrome. Anti-SRP is commonly associated with severe, acute, resistant myositis, whereas anti-Mi-2, the only MSA directed at a nuclear protein, is specifically associated with DM. Patients with anti-PM-Scl commonly have an overlap syndrome of PM/DM and SSc. Recent studies have recognized other antibodies in PM and DM, including antibody to endothelial cells, heat shock proteins, and, in a high proportion of patients, a 56-kd component of a ribonucleoprotein particle. The MSAs and their antigens are being characterized in detail. To date, data suggest similarity of predominant epitopes between different patients and a tendency toward conformational epitopes. It is not known if the recognized autoantibodies participate in tissue injury or pathogenetic processes, but production of the MSAs appears to be linked to etiologic factors and can be a clue to understanding the disease. Although these autoimmune responses are becoming better defined, the inciting events leading to generation of these responses and development of PM and DM remain unknown.