Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA.
Autoimmun Rev. 2012 Jun;11(8):604-9. doi: 10.1016/j.autrev.2011.10.022. Epub 2011 Oct 25.
Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and inflammatory bowel disease, have complex pathogeneses and likely multifactorial etiologies. The current paradigm for understanding their development is that the disease is triggered in genetically-susceptible individuals by exposure to environmental factors. Some of these environmental factors have been specifically identified, while others are hypothesized and not yet proven, and it is likely that most have yet to be identified. One interesting hypothesis is that environmental effects on immune responses could be mediated by changes in epigenetic regulation. Major mechanisms of epigenetic gene regulation include DNA methylation and histone modification. In these cases, gene expression is modified without involving changes in DNA sequence. Epigenetics is a new and interesting research field in autoimmune diseases. We review the roles of genetic factors, epigenetic regulation and the most studied environmental risk factors such as cigarette smoke, crystalline silica, Epstein-Barr virus, and reproductive hormones in the pathogenesis of autoimmune disease.
自身免疫性疾病，如类风湿关节炎、系统性红斑狼疮、多发性硬化症和炎症性肠病，具有复杂的发病机制和可能的多因素病因。目前对其发病机制的理解模式是，疾病在遗传易感个体中由环境因素暴露引发。其中一些环境因素已被明确识别，而其他因素则被假设存在但尚未得到证实，而且很可能大多数环境因素尚未被识别。一个有趣的假设是，环境对免疫反应的影响可能是通过表观遗传调控的变化来介导的。表观遗传基因调控的主要机制包括 DNA 甲基化和组蛋白修饰。在这些情况下，基因表达的改变不涉及 DNA 序列的变化。表观遗传学是自身免疫性疾病中一个新的、有趣的研究领域。我们综述了遗传因素、表观遗传调控以及最受研究的环境风险因素（如香烟烟雾、结晶二氧化硅、Epstein-Barr 病毒和生殖激素）在自身免疫性疾病发病机制中的作用。
