Steven A Greenberg1. 1. Division of Neuromuscular Disease, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. sagreenberg@partners.org
Abstract
PURPOSE OF REVIEW: To review new insights into the disease mechanisms of dermatomyositis, inclusion body myositis, and polymyositis gained from large-scale microarray gene expression studies of patient tissue samples. RECENT FINDINGS: The detection of unexpected gene transcripts using microarrays in inflammatory myopathy tissue has led to the discovery of new types and roles of immune system cells present in muscle in these diseases. Plasmacytoid dendritic cells, the immune system's professional producer of the type 1 interferons alpha and beta, are prominent in dermatomyositis muscle. Plasma cells and myeloid dendritic cells are abundant in polymyositis and inclusion body myositis muscle. Type 1 interferon induction is the single most upregulated pathological pathway genome-wide in dermatomyositis muscle and blood. In individual patients with dermatomyositis and some with polymyositis, a blood type 1 interferon-signature correlates with disease activity. SUMMARY: The identification of new cells and pathways in inflammatory myopathies has led to deeper mechanistic understanding of these diseases and potential therapeutic approaches. Through insights gained in gene expression studies, a strong scientific rationale has developed for blockade of the type 1 interferon pathway for treatment of dermatomyositis.
PURPOSE OF REVIEW: To review new insights into the disease mechanisms of dermatomyositis, inclusion body myositis, and polymyositis gained from large-scale microarray gene expression studies of patient tissue samples. RECENT FINDINGS: The detection of unexpected gene transcripts using microarrays in inflammatory myopathy tissue has led to the discovery of new types and roles of immune system cells present in muscle in these diseases. Plasmacytoid dendritic cells, the immune system's professional producer of the type 1 interferons alpha and beta, are prominent in dermatomyositis muscle. Plasma cells and myeloid dendritic cells are abundant in polymyositis and inclusion body myositis muscle. Type 1 interferon induction is the single most upregulated pathological pathway genome-wide in dermatomyositis muscle and blood. In individual patients with dermatomyositis and some with polymyositis, a blood type 1 interferon-signature correlates with disease activity. SUMMARY: The identification of new cells and pathways in inflammatory myopathies has led to deeper mechanistic understanding of these diseases and potential therapeutic approaches. Through insights gained in gene expression studies, a strong scientific rationale has developed for blockade of the type 1 interferon pathway for treatment of dermatomyositis.