Complement and autoimmunity
Complement and autoimmunity
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DOI：
10.1007/s12026-013-8422-y
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发表时间：
2013-07-01
影响因子：
4.4
通讯作者：
Perricone, Roberto
中科院分区：
文献类型：
--
作者：
Ballanti, Eleonora;Perricone, Carlo;Perricone, Roberto
补体系统是先天免疫系统的组成部分。最初认为其主要功能仅限于通过直接杀死或刺激吞噬作用来识别和消除病原体。然而，近年来，补体系统的免疫调节功能得到证实，并确定补体蛋白在调节适应性免疫和桥接先天性和适应性应答中起重要作用。当调节这种复杂酶系统的微妙机制不平衡时，补体系统可能会导致损伤，介导组织炎症。补体系统的失调参与了几种自身免疫性疾病的发病机制和临床表现，如系统性红斑狼疮、血管炎、干燥综合征、抗磷脂综合征、系统性硬化症、皮肌炎和类风湿性关节炎。补体缺乏与自身免疫性疾病的风险增加有关。由于其功能，补体系统是广泛疾病的有吸引力的治疗靶点。迄今为止，已经在自身免疫性疾病的实验模型中研究了几种干扰补体级联的化合物。主要的治疗策略是抑制补体激活成分、抑制补体受体和抑制膜攻击复合物。目前，没有一种药物被证明是安全有效的治疗人类自身免疫性疾病。尽管如此，来自临床前研究和初步临床试验的数据表明，补体系统的调节可能构成未来几十年治疗自身免疫性疾病的可行策略。
The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjogren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.