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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 69, Number 21, November 20, 2007 Data Supplement All Versions of this Article: 01.WNL.0000291619.17160.b8v1 69/21/2008    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Greenberg, S. A. Search for Related Content PubMed PubMed Citation Articles by Greenberg, S. A. Related Collections All Immunology Autoimmune diseases Muscle disease

Proposed immunologic models of the inflammatory myopathies and potential therapeutic implications

From the Department of Neurology, Division of Neuromuscular Disease, Brigham and Women’s Hospital and Harvard Medical School, Boston; and Children’s Hospital Informatics Program and Harvard-MIT Division of Health Sciences and Technology, Boston, MA.

Address correspondence and reprint requests to Dr. Steven A. Greenberg, Department of Neurology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 sagreenberg{at}partners.org

Several immune system cell types and processes have been recently identified in muscle in inclusion body myositis, dermatomyositis, and polymyositis. Plasmacytoid dendritic cells, the immune system’s professional producer of the type 1 interferons alpha and beta, are present in dermatomyositis muscle and skin. These tissues also show high expression of transcripts and proteins from genes that are induced by interferon alpha and beta. Myeloid dendritic cells, which contribute to an immunologic synapse responsible for activation of the adaptive immune system, are abundant within muscle in inclusion body myositis and polymyositis. B cells and plasma cells, effector cells of the humoral immune system, have been stimulated by antigen to transcribe immunoglobulins and produce antibodies in muscle in all three of these diseases. The presence of these immune cells and processes suggests revisions in models of the pathogenesis of the inflammatory myopathies and provides rationales for future therapeutic approaches.

Abbreviations: DC = dendritic cells; DM = dermatomyositis; FDA = Food and Drug Administration; IBM = inclusion body myositis; IFI16 = interferon-gamma inducible protein 16; IRF7 = interferon regulatory factor 7; ISG15 = interferon-stimulated gene 15; IVIg = IV immunoglobulin; LFA-3 = lymphocyte function associated antigen 3; MxA = myxovirus resistance A; pDC = plasmacytoid dendritic cell; PM = polymyositis;RER = rough endoplasmic reticulum; SLE = systemic lupus erythematosus; TCR = T cell receptor; TLR-9 = toll-like receptor 9; TNF = tumor necrosis factor alpha.

Supplemental data at www.neurology.org

Editorial, see page 1966

e-Pub ahead of print on October 10, 2007, at www.neurology.org.

Supported by grants from the Muscular Dystrophy Association, the Sporadic Inclusion Body Myositis Research Foundation, and the NIH, National Institute of Neurological Disorders and Stroke R01NS43471.

Disclosure: The author has received an honorarium and consulting fees from MedImmune, Inc.

Received December 21, 2006. Accepted in final form April 20, 2007.

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