Cell damage and autoimmunity: A critical appraisal
Cell damage and autoimmunity: A critical appraisal
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DOI：
10.1016/j.jaut.2007.11.009
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发表时间：
2008-02-01
影响因子：
12.8
通讯作者：
Rose, Noel R.
中科院分区：
文献类型：
--
作者：
Mackay, Ian R.;Leskovsek, Natasha V.;Rose, Noel R.
2007年4月，举行了一场连接科学和临床学科的国际学术研讨会，讨论细胞和组织损伤在自身免疫性疾病的发生、发展和持续中的作用。自身免疫性疾病的五个潜在病因学和病理生理学过程（即炎症、感染、细胞凋亡、环境暴露和遗传学）是研讨会上演讲和综合讨论的焦点。本综述浓缩了有关这些主题的信息。炎症与自身免疫具有密切的临床病理关联，但未来的分析将需要更好的炎症定义和指标，特别是对于依赖于先天免疫元素募集的最早的细胞和分子成分。尽管感染可能与自身抗体水平升高有关，但人类的大多数感染和几乎所有疫苗接种都与自身免疫性疾病缺乏明确的联系。迫切需要进一步应用精心设计的长期流行病学和基于人群的研究，将先前的暴露与后来发生的自身免疫的耻辱联系起来，以识别潜在的易感个体或亚群。需要仔细检查的可疑感染包括 EB 病毒（SLE 和其他疾病）、HCV（自身免疫性肝炎）、β 溶血性链球菌（风湿性心脏病）和幽门螺杆菌（自身免疫性胃炎）等。即使微生物被定罪，自身免疫的启动/持续机制仍然对研究人员构成挑战。可能的机制包括先天免疫的增强和转移；细胞内自身抗原的暴露或溢出；或提供自身抗原模拟物。细胞凋亡的完整性作为对抗自身免疫的关键保障，在过度反应导致自身抗原增强暴露于免疫系统，或反应不足导致淋巴细胞自身反应性克隆消除不足的背景下进行了讨论。尽管人们普遍认为环境因素是遗传易感个体中自身免疫性疾病的必要“触发因素”，但只有少数此类因素（主要是药物和一些营养素）已被明确识别并确定其作用机制。最后，所有这些自身免疫危害的重要遗传基础是以免疫调节基因中风险相关多态性的形式存在。它们可以预测未来或即将发生的疾病。 (C) 2007 Elsevier Ltd. 保留所有权利。
In April 2007, an international Colloquium bridging scientific and clinical disciplines was held to discuss the role of cellular and tissue damage in the initiation, development and persistence of autoimmune disease. Five potential etiologic and pathophysiologic processes fundamental to autoimmune disease (i.e. inflammation, infection, apoptosis, environmental exposure and genetics) were the focus of the presentations and integrative discussions at the Colloquium. The information presented on these topics is condensed in this review.Inflammation has close clinico-pathologic associations with autoimmunity, but future analyses will require better definition and metrics of inflammation, particularly for the earliest cellular and molecular components dependent on recruitment of elements of innate immunity. Although infection may be associated with increased levels of autoantibodies, most infections and virtually all vaccinations in humans lack well-established links to autoimmune diseases. Further application of well-designed, long-term epidemiologic and population-based studies is urgently needed to relate antecedent exposures with later occurring stigmata of autoimmunity with a goal of discerning potentially susceptible individuals or subpopulations. Suspect infections requiring closer interrogation include EB virus (SLE and other diseases), HCV (autoimmune hepatitis), beta hemolytic streptococci (rheumatic carditis) and Helicobacter pylori (autoimmune gastritis) among others. And even if a microorganism was to be incriminated, mechanisms of initiation/perpetuation of autoimmunity continue to challenge investigators. Plausible mechanisms include potentiation and diversion of innate immunity; exposure or spillage of intracellular autoantigens; or provision of autoantigenic mimics. Integrity of apoptosis as a critical safeguard against autoimmunity was discussed in the contexts of over-reactivity causing autoantigens to gain enhanced exposure to the immune system, or under-reactivity producing insufficient elimination of autoreactive clones of lymphocytes. Although environmental agents are widely believed to serve as necessary "triggers" of autoimmune disease in genetically predisposed individuals, only a few such agents (mainly drugs and some nutrients) have been clearly identified and their mechanism of action defined. Finally an essential genetic foundation underlies all these hazards for autoimmunity in the form of risk-associated polymorphisms in immunoregulatory genes. They may be predictive of future or impending disease. (C) 2007 Elsevier Ltd. All rights reserved.