Document Detail


Pathogenesis, classification and treatment of inflammatory myopathies.
MedLine Citation:
PMID:  21468145     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The inflammatory myopathies-collectively, myositis-are a heterogeneous group of chronic muscle disorders that differ in response to immunosuppressive treatment. Insufficient knowledge of the molecular pathways that drive pathogenesis (and underlie the clinical differences between subtypes) has hindered accurate classification, which in turn has been detrimental for clinical research. Nevertheless, new insights into pathogenesis are paving the way for improvements in diagnosis, classification and treatment. Accumulating data suggest that both immune and nonimmune mechanisms cause muscle weakness. Phenotyping of the T cells that accumulate in muscle tissue has identified proinflammatory, apoptosis resistant and cytotoxic CD4(+) and CD8(+) CD28(null) populations. Several myositis-specific autoantibodies have been identified, associated with distinct clinical phenotypes. Thus, adaptive immunity is involved in pathogenesis, and both T and B cells are interesting targets for therapy. Furthermore, genotyping has revealed activation of the type I interferon pathway in patients with dermatomyositis or with expression of particular autoantibodies. Decreased release of Ca(2+) from the sarcoplasmic reticulum, as a consequence of release of proinflammatory cytokines and high mobility group protein B1, might contribute to muscle weakness, and nonimmune mechanisms potentially include a role for endoplasmic reticulum stress, autophagy and hypoxia. Deeper understanding, careful phenotyping of patients-and new classification criteria-will expedite clinical research.
Authors:
Mei Zong; Ingrid E Lundberg
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-05
Journal Detail:
Title:  Nature reviews. Rheumatology     Volume:  -     ISSN:  1759-4804     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101500080     Medline TA:  Nat Rev Rheumatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
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