Revisiting the immunopathogenesis of the inflammatory myopathies

Abstract

The current classification and pathogenetic concepts of the common inflammatory myopathies, polymyositis (PM), dermatomyositis, and inclusion body myositis (IBM), has been based on clinical, histologic, and especially immunohistologic observations.1 Briefly, muscle fiber injury in dermatomyositis has been attributed to microvascular injury, possibly immune mediated, and that in PM and IBM, at least in part, to cytotoxic T-cells (CTLs). In PM and IBM, CTLs focally surround, invade, and destroy non-necrotic muscle fibers, directing perforin-containing cytotoxic granules vectorially toward the attacked fibers (figure).2 The target fibers express HLA-class I absent from normal fibers. Thus, an immunologic synapse exists between CTLs expressing T-cell receptors (TCRs) and target fibers expressing HLA-bound peptide antigens. In IBM the CTL-mediated myocytotoxicity might be related to a predisposing degenerative process. Figure Cytotoxic T cell (upper left) attacks muscle fiber (lower right) in polymyositis Note that the T cell orients its perforin-containing granules (red) toward the muscle fiber, suggesting formation of an immunologic synapse. Confocal laser image, approximately ×2,000. From reference 2 with permission of the publisher. In this issue, Dr. S.A. Greenberg3 proposes to modify traditional pathogenetic concepts of the inflammatory myopathies on the basis of novel findings that come mainly from his own work. Microarray analyses of muscle transcriptomes in different inflammatory myopathies led to several important …