This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (56)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology, Other  • Alert me on articles by topic

Marinos C. Dalakas, MD

Arch Neurol. 1998;55:1509-1512.

Polymyositis, dermatomyositis, and inclusion body myositis, although immunopathologically distinct, share 3 dominant histological features: inflammation, fibrosis, and loss of muscle fibers. Progress in molecular immunology and immunogenetics has enhanced our understanding of these cellular processes. Based on the T-cell receptor gene rearrangement, the autoinvasive CD8⁺ T cells in polymyositis and inclusion body myositis, but not dermatomyositis, are specifically selected and clonally expanded in situ by heretofore unkown muscle-specific autoantigens. The messenger RNA of cytokines is variably expressed, except for a persistent up-regulation of interleukin 1 in inclusion body myositis and transforming growth factor in dermatomyositis. In inclusion body myositis, the interleukin 1, secreted by the chronically activated endomysial inflammatory cells, may participate in the formation of amyloid because it up-regulates -amyloid precursor protein (-APP) gene expression and -APP promoter and colocalizes with -APP within the vacuolated muscle fibers. In dermatomyositis, transforming growth factor is overexpressed in the perimysial connective tissue but is down-regulated after successful immunotherapy and reduction of inflammation and fibrosis. The degenerating muscle fibers express several antiapoptotic molecules, such as Bcl-2, and resist apoptosis-mediated cell death. In myositis, several of the identified molecules and adhesion receptors play a role in the process of inflammation, fibrosis, and muscle fiber loss, and could be targets for the design of semispecific therapeutic interventions.

From the Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

A "nema" of hope in the treatment of late-onset nemaline myopathy
Dalakas and Smith
Neurology 2008;71:472-473.
FULL TEXT  

Comment on 'Interrelation of inflammation and APP in sIBM: IL-1{beta} induces accumulation of {beta}-amyloid in skeletal muscle'
Greenberg
Brain 2008;0:awn163v1-awn163.
FULL TEXT  

Inflammation interrelates to APP in sIBM: IL-1{beta} induces accumulation of {beta}-amyloid
Schmidt and Dalakas
Brain 2008;0:awn164v1-awn164.
FULL TEXT  

Interrelation of inflammation and APP in sIBM: IL-1{beta} induces accumulation of {beta}-amyloid in skeletal muscle
Schmidt et al.
Brain 2008;131:1228-1240.
ABSTRACT | FULL TEXT  

A perspective on sporadic inclusion-body myositis: The role of aging and inflammatory processes
Finch
Neurology 2006;66:S1-S6.
ABSTRACT | FULL TEXT  

Inflammatory, immune, and viral aspects of inclusion-body myositis
Dalakas
Neurology 2006;66:S33-S38.
ABSTRACT | FULL TEXT  

Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes
Raju and Dalakas
Brain 2005;128:1887-1896.
ABSTRACT | FULL TEXT  

Muscle-specific BCL2 expression ameliorates muscle disease in laminin {alpha}2-deficient, but not in dystrophin-deficient, mice
Dominov et al.
Hum Mol Genet 2005;14:1029-1040.
ABSTRACT | FULL TEXT  

Intravenous Immunoglobulin in Autoimmune Neuromuscular Diseases
Dalakas
JAMA 2004;291:2367-2375.
ABSTRACT | FULL TEXT  

Molecular profiles of inflammatory myopathies
Greenberg et al.
Neurology 2002;59:1170-1182.
ABSTRACT | FULL TEXT  

Inflammatory myositis associated with anti-U1-small nuclear ribonucleoprotein antibodies: a subset of myositis associated with a favourable outcome
Coppo et al.
Rheumatology (Oxford) 2002;41:1040-1046.
ABSTRACT | FULL TEXT  

Progress in inflammatory myopathies: good but not good enough
DALAKAS
J. Neurol. Neurosurg. Psychiatry 2001;70:569-573.
FULL TEXT  

A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM
Dalakas et al.
Neurology 2001;56:323-327.
ABSTRACT | FULL TEXT  

Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time: Studies in repeated muscle biopsies
Amemiya et al.
Brain 2000;123:2030-2039.
ABSTRACT | FULL TEXT  

Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies
Choi and Dalakas
Neurology 2000;54:65-65.
ABSTRACT | FULL TEXT  

Expression of the Costimulatory Molecule BB-1, the Ligands CTLA-4 and CD28, and their mRNA in Inflammatory Myopathies
Murata and Dalakas
Am. J. Pathol. 1999;155:453-460.
ABSTRACT | FULL TEXT