Celiac Disease: From Genetic Risk to Disease Development

乳糜泻：从遗传风险到疾病发展

• 批准号: 7371748
• 负责人: Susan L. Neuhausen
• 金额: $ 20.15万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371748
• 关键词: Abdominal Pain; Address; Adherence; Age; Anemia; Antibodies; Atrophic; Autoimmune Diseases; Barley; Biological Markers; California; Celiac Disease; Child; Chronic; Clinic; Clinical Management; Cohort Studies; Data; Development; Development, Other; Diagnosis; Diarrhea; Diet; Dietary Proteins; Disease; Early Diagnosis; Emotional Stress; Enrollment; European; Event; Failure; Family; Family Study; Family member; First Degree Relative; Frequencies; General Population; Genetic Risk; Gluten; Growth; Health; High Prevalence; Histologic; Immune System Diseases; Incidence; Individual; Infiltration; Insulin-Dependent Diabetes Mellitus; Life; Lymphocyte; Lymphoma; Malabsorption Syndromes; Minor; Morbidity - disease rate; Operative Surgical Procedures; Osteoporosis; Participant; Pernicious Anemia; Pharmacological Treatment; Population; Pregnancy; Prevalence; Principal Investigator; Public Health; Questionnaires; Range; Recontacts; Recurrence; Reporting; Rheumatoid Arthritis; Risk; Rye cereal; Sampling; Screening procedure; Seizures; Serologic tests; Serological; Serum; Small Intestines; Spontaneous abortion; Stomach; Stress; Symptoms; Testing; Thyroiditis; Time; Translations; Universities; Villus; Vitamin Deficiency; Wheat; base; cohort; disorder risk; flu; follow-up; improved; intestinal epithelium; prevent; programs

DESCRIPTION (provided by applicant): Celiac disease (CD, gluten-sensitive enteropathy, celiac sprue) is a common disease with significant morbidity if untreated. It is caused by sensitivity to the dietary protein gluten, which is present in wheat, rye and barley. The term gluten-sensitive enteropathy refers to the histologic abnormality of the small intestine. It is now recognized to be a common disease, with reports that the disease frequency is 1:150 in the US, similar to European estimates. Before the development of highly specific and sensitive antibody tests, CD was under-diagnosed. Recently, it has been proposed that in addition to better diagnosis, CD is also increasing in incidence. Occult disease is frequently present with minimal classic symptoms or signs. The ratio of symptomatic to asymptomatic CD is estimated to be 1:7. Some complications of CD include lymphoma, osteoporosis, anemia, miscarriages, seizures, vitamin deficiencies, and co-occurrence of other autoimmune diseases. No pharmacological treatment is available. Although treatment with a gluten-free diet will improve symptoms, recurrence of symptoms and complications may occur after minor dietary indiscretions. There are several unaddressed public health concerns that will be focused on in this proposal. Do individuals at high risk of CD warrant continued screening and are there putative stress events that trigger the disease in susceptible individuals? Does the early detection of CD by screening reduce the risk of development of additional autoimmune disorders that are known to be associated with CD? Are individuals diagnosed with CD at higher risk of developing other autoimmune diseases and additional symptoms if they do not adhere to a gluten-free diet? To investigate these questions, we will recontact individuals previously enrolled in two family studies, one at the University of California Irvine and one at Mayo Clinic, in which we had systematically performed serologic and HLA testing and collected symptom data for family members from CD families. Aim 1 is to investigate the development of CD in first-degree relatives of CD cases who previously tested negative five or more years ago. We will perform serologic testing for CD and have the subjects complete a follow-up questionnaire including data items on general health, CD symptoms, associated-diseases, diet, and major life events as potential triggers for CD. Aim 2 is to investigate the prevalence of auto-antibodies that serve as biomarkers for thyroiditis, type I diabetes, pernicious anemia, and rheumatoid arthritis in CD cases. We will obtain new sera and follow-up questionnaires from CD cases diagnosed at least five years ago. This study will address two critical public health management issues in CD: 1) whether retesting is necessary for those at high-risk who have previously tested negative; and 2) whether the association of CD with other auto-immune diseases can be mitigated by following a gluten-free diet. These results will provide information to facilitate translation into clinical management of the disease and its comorbid conditions.This proposal is focused on the public health implications of celiac disease, a common disease with a population prevalence of 1:150 in the US. First, we will determine whether a single test for celiac disease in individuals at high risk of disease is adequate or whether repeat testing is necessary. Second, we will determine the impact of celiac disease on the development of other autoimmune diseases, and whether adherence to a gluten-free diet can prevent development, delay onset, or reduce symptoms of other auto-immune diseases.

描述（由申请人提供）：乳糜泻（CD、麸质敏感性肠病、乳糜泻）是一种常见疾病，如果不治疗，发病率很高。它是由对小麦、黑麦和大麦中存在的膳食蛋白麸质敏感引起的。术语麸质敏感性肠病是指小肠的组织学异常。现在它被认为是一种常见疾病，据报道，在美国该病的发病率为 1:150，与欧洲的估计相似。在开发出高度特异性和敏感性的抗体测试之前，克罗恩病的诊断不足。最近，有人提出，除了更好的诊断外，克罗恩病的发病率也在增加。隐匿性疾病常常以最小的典型症状或体征出现。有症状与无症状 CD 的比例估计为 1:7。 CD 的一些并发症包括淋巴瘤、骨质疏松症、贫血、流产、癫痫发作、维生素缺乏以及其他自身免疫性疾病的并发。没有可用的药物治疗。尽管无麸质饮食治疗可以改善症状，但轻微的饮食不检点后可能会出现症状和并发症的复发。本提案将重点关注几个尚未解决的公共卫生问题。患有克罗恩病的高风险个体是否值得继续筛查？是否存在推定的应激事件会在易感个体中引发该疾病？通过筛查早期发现 CD 是否可以降低罹患已知与 CD 相关的其他自身免疫性疾病的风险？如果不坚持无麸质饮食，被诊断患有 CD 的个体患其他自身免疫性疾病和其他症状的风险是否会更高？为了调查这些问题，我们将重新联系之前参加两项家庭研究的个人，一项在加州大学欧文分校，另一项在梅奥诊所，在这两项研究中，我们系统地进行了血清学和 HLA 检测，并收集了 CD 家族家庭成员的症状数据。目标 1 是调查五年前或五年前检测呈阴性的 CD 病例的一级亲属中 CD 的发展情况。我们将对克罗恩病进行血清学检测，并让受试者完成一份后续调查问卷，包括一般健康状况、克罗恩病症状、相关疾病、饮食和作为克罗恩病潜在触发因素的主要生活事件的数据项。目标 2 是调查 CD 病例中作为甲状腺炎、I 型糖尿病、恶性贫血和类风湿性关节炎生物标志物的自身抗体的流行情况。我们将从至少五年前诊断的克罗恩病病例中获取新的血清和后续调查问卷。这项研究将解决CD中的两个关键公共卫生管理问题：1）对于先前检测呈阴性的高危人群是否有必要重新检测； 2）是否可以通过遵循无麸质饮食来减轻克罗恩病与其他自身免疫性疾病的关联。这些结果将提供信息，以促进将该疾病及其合并症转化为临床管理。该提案的重点是乳糜泻对公共卫生的影响，乳糜泻是一种常见疾病，在美国人口患病率为 1:150。首先，我们将确定对疾病高风险个体进行一次乳糜泻检测是否足够，或者是否有必要进行重复检测。其次，我们将确定乳糜泻对其他自身免疫性疾病发展的影响，以及坚持无麸质饮食是否可以预防其他自身免疫性疾病的发展、延迟发病或减轻症状。