Immunology, Inflammation, and Endometriosis

描述(由研究人员提供)：子宫内膜异位症仍然是最神秘的妇科病理之一，其影响可能会使身体和精神虚弱。子宫内膜异位症可能不仅依赖于循环中的类固醇激素，还依赖于异常的免疫反应。病例对照研究已经观察到子宫内膜异位症患者腹腔液和血清中生长因子、巨噬细胞和促炎细胞因子的异常水平和功能。一些研究表明，患有子宫内膜异位症的女性患自身免疫性疾病的风险增加。免疫功能障碍和炎症也与糖尿病和心血管疾病的风险增加有关。最近的研究表明，子宫内膜异位症患者存在胰岛素抵抗和血管炎症。与子宫内膜异位症相关的纤溶异常可能会增加动脉斑块形成和随后的缺血性心血管疾病的风险。在护士健康研究II中观察到了2000多例经腹腔镜确诊的子宫内膜异位症病例，在黑人妇女健康研究中观察到500多例，这些前瞻性队列研究始于1989年的116,000名妇女和1995年的59,000名妇女。在20世纪90年代末，NHSII收集并存储了30,000名参与者的血液样本，其中200多人后来被诊断为子宫内膜异位症。我们提出第一项前瞻性研究来评估以下假设：目的1：炎症与子宫内膜异位症有关。具体地说，较高的内源性C反应蛋白、IL-12、IL-6、sTNFR1和sTNFR2可溶性受体水平增加了子宫内膜异位症的风险。目的2：子宫内膜异位症妇女患自身免疫性疾病的风险更高，包括类风湿性关节炎、系统性红斑狼疮(SLE)和Grave病。目的3：患有子宫内膜异位症的妇女表现出炎症和纤溶病理相关的慢性疾病的体征和更大的风险。具体地说，a)较高的内源性C-肽、胰岛素、瘦素水平和较低的脂联素水平增加了子宫内膜异位症的风险。B)患有子宫内膜异位症的女性患高血压、高胆固醇血症、2型糖尿病、心肌梗死和缺血性中风的风险更高。C)与“谨慎”饮食相比，那些饮食中含有高血糖负荷，且饮食模式与“西方”饮食相一致的人患子宫内膜异位症的风险更大。这些数据为大规模、前瞻性地研究子宫内膜异位症的危险因素和后果提供了独特的机会。公共卫生相关性子宫内膜异位症可使身体和精神衰弱，并可能与自身免疫和心血管疾病风险增加有关。我们建议对护士健康研究II中的116,000名妇女和黑人妇女健康研究中的59,000名妇女进行大规模前瞻性队列研究，以了解免疫和炎症环境如何通过生物标记物分析与子宫内膜异位症相关，以及与随后的慢性疾病的关系。我们认为，量化这些因素可能会提高我们对子宫内膜异位症的病因和后果的理解。

DESCRIPTION (provided by investigator): Endometriosis remains one of the most enigmatic gynecologic pathologies, the effects of which can be physically and mentally debilitating. Endometriosis is likely dependent not only on circulating steroid hormones but also on aberrant immunologic response. Case-control studies have observed abnormal levels and function of growth factors, macrophages, and pro-inflammatory cytokines in the peritoneal fluid and serum of women with endometriosis. A few studies suggest increased risk of autoimmune diseases among women with endometriosis. Immune dysfunction and inflammation are also associated with increased risk of diabetes mellitus and cardiovascular disease. Recent studies suggest insulin resistance and vascular inflammation among those with endometriosis. Abnormalities in fibrinolysis associated with endometriosis may increase the risk of arterial plaque formation and consequent ischemic cardiovascular disease. Over 2000 laparoscopically-confirmed incident cases of endometriosis have been observed within the Nurses' Health Study II, and over 500 within the Black Women's Health Study ongoing, prospective cohort studies that began when 116,000 women were enrolled in 1989 and 59,000 in 1995, respectively. In the late 1990s, the NHSII collected and stored blood samples from 30,000 participants, of whom more than 200 were subsequently diagnosed with endometriosis. We propose the first prospective study to assess the following hypotheses: Aim 1: Inflammation is associated with endometriosis. Specifically, higher endogenous levels of C-reactive protein, IL-12, IL-6, and sTNFR1 and sTNFR2 soluble receptors increase the risk of endometriosis. Aim 2: Women with endometriosis are at greater risk of autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and Grave's disease. Aim 3: Women with endometriosis exhibit signs of and are at greater risk for chronic diseases associated with inflammation and fibrinolytic pathology. Specifically, a) Higher endogenous levels of c-peptide, insulin, leptin, and lower levels of adiponectin increase the risk of endometriosis. b) Women with endometriosis are at greater risk of hypertension, hypercholesterolemia, type 2 diabetes, myocardial infarction, and ischemic stroke. c) Those with a diet that includes a high glycemic load and of a pattern consistent with a "western" diet compared to a "prudent" diet are at greater risk of endometriosis. These data present a unique opportunity for large-scale, prospective study of the risk factors and consequences of endometriosis. PUBLIC HEALTH RELEVANCE Endometriosis can be physically and mentally debilitating and may be associated with increased risk of autoimmune and cardiovascular disease. We propose to study over 116,000 women in the Nurses' Health Study II and 59,000 women in the Black Women's Health Study both large, prospective cohorts to learn how immunologic and inflammatory milieu relates to endometriosis via biomarker assay and association with subsequent chronic diseases. We believe that quantifying these factors may improve our understanding of the etiology and consequences of endometriosis.