Chronic Fatigue Syndrome, Immune Dysregulation, and Non-Hodgkin's Lymphoma

慢性疲劳综合症、免疫失调和非霍奇金淋巴瘤

• 批准号: 8688387
• 负责人: Roxana Moslehi
• 金额: $ 27.34万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8688387
• 关键词: Acute; Affect; Age; Antibodies; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Back; Biological; Biological Markers; Chronic; Chronic Fatigue Syndrome; Clinic; Clinical; DNA-Directed DNA Polymerase; Diagnosis; Disease; Early Diagnosis; Early treatment; Elderly; Epidemiologic Studies; Epidemiology; Ethnic Origin; Etiology; Family; Family health status; Family member; Frequencies; Gender; Generations; Genetic; Genetic Counseling; Genetic Predisposition to Disease; Geographic Locations; Hashimoto Disease; Health; High Prevalence; Human Herpesvirus 4; Immune; Immune System Diseases; Immunologic Factors; Immunologic Tests; Immunologics; Immunology procedure; Inflammatory; Inflammatory Bowel Diseases; Internal Medicine; Interview; Investigation; Laboratories; Lead; Link; Lupus; Malignant Neoplasms; Medical; Molecular; Multiple Sclerosis; Nevada; Non-Hodgkin' s Lymphoma; Participant; Patients; Population; Prevalence; Prevention; Professional counselor; Proteins; Public Health; Publications; Recording of previous events; Recruitment Activity; Relative (related person); Reporting; Research; Rheumatoid Arthritis; Risk; Role; Sampling; Scleroderma; Second Degree Relative; Source; Structure; Syndrome; Telephone Interviews; Testing; Training; United States; Viral; Virus; Vitiligo; base; cancer risk; cancer type; case control; case-based; cohort; deoxyuridine triphosphate; design; innovation; insight; interest; public health relevance; stem

DESCRIPTION (provided by applicant): The etiology of chronic fatigue syndrome (CFS), a disabling disorder affecting more than one million people in the United States (U.S.), is unknown. CFS appears to be a heterogeneous disorder with a variety of clinical presentations and postulated mechanisms. Several observations have suggested an association between CFS, immune dysregulation, autoimmune disorders (AID), and elevated risk of cancer, specifically non-Hodgkin's lymphoma (NHL). We have designed a molecular epidemiologic investigation to explore the role of genetic predisposition and specific immune factors in the etiology of CFS using a well-defined cohort of patients. We will also be studying the association between CFS and AID as well as the potential link between CFS and risk of cancer in general and NHL in particular among this population. The cases in our study will be ascertained from a pool of CFS cases diagnosed with acute onset following an infectious illness at Sierra Internal Medicine, a clinic in Nevada. Healthy (i.e., with no personal history of CFS, AID or cancer) unrelated controls have been ascertained and frequency-matched to cases by age, gender, ethnicity and geographic area. So far, 54 CFS cases fitting the criteria for diagnosis and 54 appropriately- matched controls have been pre-selected and will be approached for participation into the proposed study. In addition, we will identify healthy (i.e., with no personal history of CFS, AID or cancer) first- or second-degree relatives of CFS cases (at least one relative per case) who will be matched to cases by age, gender, ethnicity and geographic area for comparison to the cases and controls with respect to the immunologic factors pertaining to viral reactivation. Complete family health history and epidemiologic and medical information will be obtained on all participants through structured telephone interviews by a research assistant with training in genetic counseling. Cases and controls will be compared with respect to the prevalence of autoimmune disorders and specific types of cancer such as NHL among their extended relatives. Biological samples will be obtained from all subjects (cases, relatives of cases and the controls) for comparison with respect to the levels of antibodies against Epstein Barr Virus (EBV)-encoded proteins, namely EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTP- ase) and DNA polymerase. Our study has the potential to provide insight into the etiology of CFS and provide clues as to whether CFS is an AID through investigation of the potential genetic and immunologic link between CFS and AID among the family members. Furthermore, our study may provide insight into the association between CFS and NHL. The public health impact of our study stems from its potential to lead to early diagnosis and/or treatment of CFS, AID and NHL through understanding the etiologic link between these disorders and the role of genetic and immunologic factors.

描述（由申请人提供）：慢性疲劳综合征（CFS）的病因，这是一种影响美国（U.S.）100多万人的致残性疾病，不明CFS似乎是一种异质性疾病，具有多种临床表现和假定机制。一些观察结果表明CFS、免疫失调、自身免疫性疾病（AID）和癌症（特别是非霍奇金淋巴瘤（NHL））风险升高之间存在关联。我们设计了一个分子流行病学调查，以探讨遗传易感性和特定的免疫因素在CFS的病因学中的作用，使用一个明确的患者队列。我们还将研究CFS和艾滋病之间的关联，以及CFS和癌症风险之间的潜在联系，特别是在这一人群中的NHL。我们研究中的病例将从内华达州的一家诊所Sierra Internal Medicine诊断为感染性疾病后急性发作的CFS病例库中确定。健康（即，没有CFS、AID或癌症的个人病史）的不相关对照，并按年龄、性别、种族和地理区域与病例频率匹配。到目前为止，已经预先选择了54例符合诊断标准的CFS病例和54例适当匹配的对照，并将与参与拟议研究的人接触。此外，我们将识别健康的（即，没有CFS、AID或癌症的个人病史）CFS病例的一级或二级亲属（每个病例至少一名亲属），他们将根据年龄、性别、种族和地理区域与病例匹配，以与病例和对照进行关于与病毒再活化有关的免疫学因素的比较。将由一名接受过遗传咨询培训的研究助理通过结构化电话访谈获得所有参与者的完整家族健康史以及流行病学和医学信息。将比较病例和对照组的自身免疫性疾病和特定类型癌症（如NHL）在其远亲中的患病率。将从所有受试者（病例、病例亲属和对照）中获得生物样本，用于比较针对爱泼斯坦巴尔病毒（EBV）编码蛋白（即EBV编码的脱氧尿苷三磷酸核苷酸水解酶（dUTP-酶）和DNA聚合酶）的抗体水平。我们的研究有可能提供深入了解CFS的病因，并通过调查CFS和家庭成员中的AID之间的潜在遗传和免疫学联系，提供CFS是否是一种AID的线索。此外，我们的研究可能会提供深入了解CFS和NHL之间的关联。我们的研究对公共卫生的影响源于它有可能通过了解这些疾病之间的病因联系以及遗传和免疫因素的作用来早期诊断和/或治疗CFS，AID和NHL。