Molecular immunology and genetics of inflammatory muscle diseases

Polymyositis, dermatomyositis, and inclusion body myositis, although immuno pathologically distinct, share 3 dominant histological features: inflammati on, fibrosis, and loss of muscle fibers. Progress in molecular immunology a nd immunogenetics has enhanced our understanding of these cellular processe s. Based on the T-cell receptor gene rearrangement, the autoinvasive CD8(+) T cells in polymyositis and inclusion body myositis, but not dermatomyosit is, are specifically selected and clonally expanded in situ by heretofore u nkown muscle-specific autoantigens. The messenger RNA of cytokines is varia bly expressed, except for a persistent up-regulation of interleukin 1 beta in inclusion body myositis and transforming growth factor beta in dermatomy ositis. In inclusion body myositis, the interleukin 1, secreted by the chro nically activated endomysial inflammatory cells, may participate in the for mation of amyloid because it up-regulates beta-amyloid precursor protein (b eta-APP) gene expression and beta-APP promoter and colocalizes with beta-AP P within the vacuolated muscle fibers. In dermatomyositis, transforming gro wth factor beta is overexpressed in the perimysial connective tissue but: i s down-regulated after successful immunotherapy and reduction of inflammati on and fibrosis. The degenerating muscle fibers express several antiapoptot ic molecules, such as Bcl-2, and resist apoptosis-mediated cell death. In m yositis, several of the identified molecules and adhesion receptors play a role in the process of inflammation, fibrosis, and muscle fiber loss, and c ould be targets for the design of semispecific therapeutic interventions.