Humoral immunity and immunogenetics in the idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare but increasingly recognized syndromes characterized by chronic muscle inflammation of unknown cause. The finding of other autoimmune diseases in association with IIM, the inflammatory pathology, the response to immunosuppressive therapy, and the frequent occurrence of autoantibodies all support the notion that the IIMs are autoimmune diseases. IIM patients are unique in their immune targeting of a group of autoantigens involved in protein synthesis. Recent studies of the autoantibodies that bind these autoantigens (the myositis-specific autoantibodies) suggest that they arise by mechanisms that closely resemble standard immune responses. There is increasing interest in and efforts directed toward dividing the rheumatic diseases into more uniform groups for purposes of better defining etiology and pathogenesis. This approach has been useful in the analysis of the IIMs in which new approaches, subsetting patients by autoantibodies, have produced more homogeneous groupings. Recent data on predisposing immunogenetic factors in different clinical and serologic subsets of IIM patients also suggest that these disorders result from environmental agents acting on groups of genetically restricted individuals to induce immunologic activation and subsequent tissue pathology. This review summarizes these findings about the origins of the myositis-specific autoantibodies and their epidemiologic, clinical, prognostic, and immunogenetic associations.