补体活化与多种常见的风湿性疾病相关,例如系统性红斑狼疮(SLE),类风湿关节炎(RA),和系统性血管炎。
摘 要
补体活化与多种常见的风湿性疾病相关,例如系统性红斑狼疮(SLE),类风湿关节炎(RA),和系统性血管炎。
补体激活与这些疾病相关的证据包括在这些疾病患者以及实验动物的受累组织中有补体沉积,补体蛋白水平降低,血和/或滑液中补体活化片段水平升高。
Eculizumab,一种抑制补体C5的单克隆抗体,目前已经批准用于一些少见情况的治疗,包括补体过度活化,这种治疗的成功已经引起在风湿实践中应用补体抑制治疗的新兴趣,特别是对系统性红斑狼疮。例如,抑制C5是减少狼疮肾炎的肾小球炎症或治疗血栓性微血管病的潜在方法。
补体系统是复杂性疾病例如SLE导致组织损伤的众多因素之一,确定补体激活在疾病中发挥主要作用具有一定的挑战性。RA的另一个困难是在已有的各种治疗模式下,确定治疗性补体抑制的作用。在本篇综述中,对风湿病治疗中抑制补体治疗潜力的证据进行了评价。
原 文
Abstract
Complement activation is associated withcommon rheumatic diseases such as systemic lupus erythematosus(SLE),rheumatoid arthritis(RA) and systemic vasculitis. Evidence linkingcomplement activation to these diseases includes the presence of complementdeposition in affected tissues, decreased levels of complement proteins andhigh levels of complement activation fragments in the blood and/or synovialfluid of patients with these diseases, as well as data from experimentalmodels. Eculizumab, a monoclonal antibody that inhibits the complementcomponent C5, is now approved for the treatment of rare conditions involvingcomplement hyperactivation, and the success of this therapy has renewedinterest in understanding the utility of complement inhibition in rheumatologicalpractice, particularly for SLE. For example, inhibiting C5 is a potential meansof reducing glomerular inflammation in lupus nephritis or treating thromboticmicroangiopathy in SLE. The complement system is one of multiple mediators oftissue injury in complex diseases such as SLE, and identifying the diseasecontext in which complement activation has a predominant role is a challenge.An added difficulty in RA is identifying a role for therapeutic complementinhibition within the diverse treatment modalities already available. In thisReview, evidence for the therapeutic potential of complement manipulation inrheumatology practice is evaluated.
引自:Trouw LA,Pickering MC,Blom AM.The complement system as a potential therapeutic target in rheumaticdisease. Nat Rev Rheumatol.2017 Aug 10.doi: 10.1038/nrrheum.2017.125. [Epub ahead of print]
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