Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health Clinical Research Center, Bethesda, MD 20892-1301, USA.
J Autoimmun. 2012 Dec;39(4):259-71. doi: 10.1016/j.jaut.2012.05.002. Epub 2012 Jun 25.
Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.
自身免疫性疾病（AID）是一组病因不明的多种复杂疾病，导致针对自身抗原的免疫反应，被认为是遗传和环境因素相互作用的结果。在这里，我们回顾了环境因素在人类 AID 发展中的作用的流行病学证据，从现有数据中可以得出的结论，关键的知识差距，以及填补这些差距和解决不确定性所需的研究。我们特别总结了特定代理在自身免疫性疾病发展中的作用的知识现状和我们的置信度水平，并确定了未来调查的最大影响领域。在我们的共识发现中，我们有信心：1）晶体二氧化硅暴露可能导致几种 AID 的发展；2）溶剂暴露可能导致系统性硬化症的发展；3）吸烟可能导致血清阳性类风湿关节炎的发展；4）紫外线辐射暴露与多发性硬化症的发病风险呈负相关。我们建议需要更多研究表型、基因型和多种暴露。需要进一步研究的其他知识差距包括：定义暴露和与年龄、发育状态和激素变化相关的潜伏期的重要窗口；了解剂量-反应关系；阐明疾病发展的机制。解决这些重要问题将需要更多资源来支持研究，特别是罕见的 AID，但在特定遗传背景下了解环境因素带来的风险可能为未来预防 AID 铺平道路。
