Emerging therapies for systemic lupus erythematosus 鈥?Focus on targeting interferon-alpha

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• 作者：Eben I. Lichtman^a ; ^b ; Simon M. Helfgott^a ; Martin A. Kriegel^a ; ^{mkriegel@partners.org}
• 关键词：pDC ; TLR ; IRF ; Pin1 ; Virome ; Proteasome
• 刊名：Clinical Immunology
• 出版年：2012
• 期刊代码：95_15216616
• 类别：imm
• 出版时间：June, 2012
• 卷：143
• 期：3
• 页码：210-221
• 文件大小：299 K

摘要

Current therapies for systemic lupus erythematosus (SLE), a debilitating, potentially lethal, multifactorial systemic autoimmune disease, are limited to suppressing disease activity and are associated with multiple adverse effects. Recent advances in basic and translational sciences have elucidated a crucial role for the interferon-alpha (IFN伪) pathway in the pathogenesis of this enigmatic disease. The so-called 鈥渢ype I interferon signature鈥?has emerged as a major risk factor for disease activity of SLE. Multiple genes encoding for molecules within the type I interferon pathway have been associated with SLE in genome wide association studies. In addition, innate immune receptors are thought to be triggered by either endogenous and/or exogenous stimuli that lead to hypersecretion of IFN伪. We review the multiple emerging treatment strategies targeting IFN伪-related pathways. These include monoclonal antibodies against IFN伪, anti-IFN伪 antibody-inducing vaccines, and inhibitors of Toll-like receptors. We also summarize the current status of these pharmaceutical agents in early clinical trials.