Inflammatory disorders of muscle: progress in polymyositis, dermatomyositis and inclusion body myositis.
OBJECTIVE
To provide an update on the major advances in inflammatory myopathies.


RESULTS
Polymyositis is an uncommon disorder that can be misdiagnosed when the old, and never validated, criteria of Bohan and Peter are used. New diagnostic criteria were recently introduced, in which the MHC/CD8 complex is considered a specific immunopathological marker because it distinguishes the antigen-driven inflammatory cells that characterize polymyositis and sporadic inclusion-body myositis from the non-specific, secondary inflammation seen in other disorders, such as dystrophies. In sporadic inclusion-body myositis the inflammatory cells invade non-vacuolated fibers, whereas the vacuolated fibers are not invaded by T cells, implying two independent processes, a primary immune process with antigen-driven T cells identical to polymyositis, and a degenerative process in which beta-amyloid and amyloid-related proteins participate in vacuolar degeneration. In polymyositis and sporadic inclusion-body myositis, antigen-specific and clonally expanded autoinvasive T cells persist for years, even in different muscles, as reconfirmed by proof-of-principle techniques involving CDR3 spectratyping combined with laser microdissected single-cell polymerase chain reaction of the T-cell receptor genes. The formation of immunological synapse between autoinvasive T cells and muscle fibers was recently strengthened by the upregulation of co-stimulatory molecules ICOS/ICOS-L and PD-L1. A new, distinct myopathy characterized by T-cell-triggered macrophage hyperactivation has now been recognized in patients with dermatomyositis-like disease.


CONCLUSIONS
Despite recent progress, the antigen(s) responsible for T-cell activation in polymyositis and sporadic inclusion-body myositis and the cause of vacuolar degeneration in sporadic inclusion-body myositis remain unclear. Newer, more aggressive immunotherapies may be encouraging, but control trials are needed to prove efficacy.
Dalakas
Marinos C
MC
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1382, USA. dalakasm@ninds.nih.gov
D000682:Amyloid / Q000276:immunology; D003882:Dermatomyositis / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D018482:Muscle, Skeletal / Q000276:immunology / Q000503:physiopathology; D018979:Myositis, Inclusion Body / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D017285:Polymyositis / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D014617:Vacuoles / Q000276:immunology
D000682:Amyloid