The molecular and cellular pathology of inflammatory muscle diseases.
The inflammatory muscle diseases dermatomyositis, polymyositis and inclusion body myositis are of unknown cause, but immune mechanisms are strongly implicated. Progress in the past two years has led to an improved understanding of the main molecular events involved in the immunological synapse between muscle and autoinvasive T cells. In particular, we now have a better understanding of TCR gene rearrangement in endomysial T cells, regulation of MHC expression, activity of co-stimulatory molecules, and the signalling cascades activated by cytokines, chemokines and metalloproteinases. Recent reports of an upregulation of strong anti-apoptotic molecules on the surface of muscle fibers identifies the end result of these disease processes, loss of muscle cells, as through necrosis, and not apoptosis. Such progress in molecular immunopathology has generated the interest to apply semispecific immunotherapies with the hope of halting disease progression or improving the strength of patients unresponsive to currently available non-specific immunotherapeutic interventions.
Dalakas
M C
MC
Neuromuscular Diseases Section, National Institute of Neurological Disorders, National Institutes of Health, Bethesda, MD 20892-1382, USA. dalakasm@ninds.nih.gov
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D018925:Chemokines / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000502:physiology; D019672:Genes, T-Cell Receptor / Q000235:genetics; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology*; D009220:Myositis / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D018925:Chemokines; D016207:Cytokines; D020782:Matrix Metalloproteinases