Immunology, Inflammation, and Endometriosis

免疫学、炎症和子宫内膜异位症

• 批准号: 7528792
• 负责人: STACEY ANN MISSMER
• 金额: $ 36.33万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7528792
• 关键词: Abdominal Cavity; Adhesions; Autoimmune Diseases; Autoimmune Process; Biological Assay; Biological Markers; Blood specimen; Brain; C-reactive protein; Cardiovascular Diseases; Case Study; Case-Control Studies; Chronic Disease; Cicatrix; Cohort Studies; Cues; Data; Development; Diabetes Mellitus; Diagnosis; Diet; Disease; Dysmenorrhea; Dyspareunia; Dysuria; Endometrial; Enrollment; Etiology; Exhibits; Eye; Fibrinolysis; Functional disorder; Future; Graves' Disease; Growth Factor; Gynecologic; Gynecologic Pathology; Health Care Costs; Heart; Hemorrhage; Hormonal; Hospitalization; Human; Hypertension; Immune; Immune System Diseases; Immunologics; Immunology; Implant; Infertility; Inflammation; Inflammatory; Insulin; Insulin Resistance; Interleukin-12; Interleukin-6; Ischemic Stroke; Learning; Leptin; Lesion; Lung; Menstrual cycle; Morbidity - disease rate; Myocardial Infarction; Nasal cavity; Non-Insulin-Dependent Diabetes Mellitus; Nurses' Health Study; Pain; Participant; Pathology; Pattern; Pelvis; Peptides; Peritoneal Fluid; Prospective Studies; Research Personnel; Rheumatoid Arthritis; Risk; Risk Factors; Serum; Signs and Symptoms; Systemic Lupus Erythematosus; Time; Tissues; United States; Uterine cavity; Uterus; Woman; Women' s Health; adiponectin; cardiovascular risk factor; cohort; cost; cytokine; disease diagnosis; disorder risk; endometriosis; hypercholesterolemia; improved; macrophage; mortality; prospective; public health relevance; receptor; response; steroid hormone; vascular inflammation

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.

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之一，其影响可能会导致身体和精神衰弱。子宫内膜异位症可能不仅取决于循环类固醇激素，还取决于异常的免疫反应。病例对照研究观察到子宫内膜异位症女性腹膜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之而来的缺血性心血管疾病的风险。护士健康研究 II 中观察到了 2000 多例腹腔镜确诊的子宫内膜异位症病例，正在进行的黑人妇女健康研究中观察到了 500 多例，前瞻性队列研究开始于 1989 年和 1995 年分别招募了 116,000 名妇女和 59,000 名妇女。 20 世纪 90 年代末，NHSII 收集并储存了 30,000 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。我们提出第一项前瞻性研究来评估以下假设： 目标 1：炎症与子宫内膜异位症相关。具体而言，较高内源水平的 C 反应蛋白、IL-12、IL-6 以及 sTNFR1 和 sTNFR2 可溶性受体会增加子宫内膜异位症的风险。目标 2：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) 和格雷夫氏病。目标 3：患有子宫内膜异位症的女性表现出与炎症和纤溶病理相关的慢性疾病的迹象，并且患慢性疾病的风险更大。具体来说，a) 较高的内源性水平的 c 肽、胰岛素、瘦素和较低水平的脂联素会增加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大。 c) 与“谨慎”饮食相比，那些饮食包含高血糖负荷且符合“西方”饮食模式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能会导致身体和精神衰弱，并可能与自身免疫和心血管疾病的风险增加有关。我们建议对护士健康研究 II 中的 116,000 多名女性和黑人女性健康研究中的 59,000 名女性进行研究，这两个大型前瞻性队列都是通过生物标志物测定以及与随后的慢性疾病的关联来了解免疫和炎症环境与子宫内膜异位症的关系。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。