Immunology, Inflammation, and Endometriosis

描述（由研究者提供）：子宫内膜异位症仍然是最神秘的妇科病理学之一，其影响可使身体和精神衰弱。子宫内膜异位症可能不仅依赖于循环类固醇激素，也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水平和功能异常。一些研究表明子宫内膜异位症妇女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，胰岛素抵抗和血管炎症与子宫内膜异位症。与子宫内膜异位症相关的纤维蛋白溶解的减少可能增加动脉斑块形成和随之发生的缺血性心血管疾病的风险。在护士健康研究II中观察到超过2000例腹腔镜证实的子宫内膜异位症事件病例，在黑人妇女健康研究中观察到超过500例，前瞻性队列研究分别于1989年和1995年招募了116，000名妇女和59，000名妇女。在20世纪90年代末，NHSII收集并储存了3万名参与者的血液样本，其中200多人随后被诊断患有子宫内膜异位症。我们提出了第一个前瞻性研究，以评估以下假设：目的1：炎症与子宫内膜异位症。特别是，C-反应蛋白、IL-12、IL-6、sTNFR 1和sTNFR 2可溶性受体的内源性水平升高会增加子宫内膜异位症的风险。目标二：患有子宫内膜异位症的女性患自身免疫性疾病的风险更大，包括类风湿性关节炎，系统性红斑狼疮（SLE）和格雷夫斯病。目的3：子宫内膜异位症妇女表现出与炎症和纤溶病理相关的慢性疾病的迹象，并有更大的风险。具体来说，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子宫内膜异位症的风险。B）子宫内膜异位症的妇女患高血压、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大。c）那些饮食包括高血糖负荷和与“西方”饮食相一致的模式的人与“谨慎”饮食相比，患子宫内膜异位症的风险更大。这些数据为子宫内膜异位症的危险因素和后果的大规模前瞻性研究提供了独特的机会。子宫内膜异位症可使身体和精神衰弱，并可能与自身免疫性和心血管疾病的风险增加有关。我们建议在护士健康研究II中研究超过116，000名妇女，在黑人妇女健康研究中研究59，000名妇女，这两个大型前瞻性队列研究通过生物标志物测定了解免疫和炎症环境如何与子宫内膜异位症相关以及与随后的慢性疾病的相关性。我们相信，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.