Type I interferon in organ-targeted autoimmune and inflammatory diseases.
Type I interferon in organ-targeted autoimmune and inflammatory diseases.
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DOI：
10.1186/ar2886
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发表时间：
2010
影响因子：
4.9
通讯作者：
Crow MK
中科院分区：
文献类型：
--
作者：
Crow MK
干扰素α在系统性红斑狼疮发病机制中的重要作用得到了很好的支持，抗干扰素α单抗的临床试验正在进行中。在以大量炎症和组织破坏为特征的其他自身免疫性疾病中，I型干扰素的作用不太清楚。类风湿性关节炎和多发性硬化症患者外周血细胞的基因表达分析表明，干扰素信号类似于狼疮患者，但强度低于狼疮患者。在这两种疾病中，干扰素信号的存在与更显著的临床表现有关。与此同时，有证据表明，干扰素β在类风湿关节炎患者的关节和小鼠关节炎模型中具有局部抗炎和有益作用，许多多发性硬化症患者对重组干扰素β表现出临床反应。对于I型糖尿病也可以提出，I型干扰素似乎有助于多种自身免疫性疾病的自身免疫的发展和疾病的进展，同时保持一定的控制既定疾病的能力--特别是在局部炎症部位。最近对类风湿性关节炎和多发性硬化症的研究表明，I型干扰素活性或靶基因表达的量化可能有助于预测对不同类别治疗药物的反应。
A significant role for IFNα in the pathogenesis of systemic lupus erythematosus is well supported, and clinical trials of anti-IFNα monoclonal antibodies are in progress in this disease. In other autoimmune diseases characterized by substantial inflammation and tissue destruction, the role of type I interferons is less clear. Gene expression analysis of peripheral blood cells from patients with rheumatoid arthritis and multiple sclerosis demonstrate an interferon signature similar to but less intense than that seen in patients with lupus. In both of those diseases, presence of the interferon signature has been associated with more significant clinical manifestations. At the same time, evidence supports an anti-inflammatory and beneficial role of IFNβ locally in the joints of patients with rheumatoid arthritis and in murine arthritis models, and many patients with multiple sclerosis show a clinical response to recombinant IFNβ. As can also be proposed for type I diabetes mellitus, type I interferon appears to contribute to the development of autoimmunity and disease progression in multiple autoimmune diseases, while maintaining some capacity to control established disease - particularly at local sites of inflammation. Recent studies in both rheumatoid arthritis and multiple sclerosis suggest that quantification of type I interferon activity or target gene expression might be informative in predicting responses to distinct classes of therapeutic agents.