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

描述(申请人提供)：慢性疲劳综合症(CFS)是一种影响美国100多万人的致残障碍，其病因尚不清楚。CFS似乎是一种具有多种临床表现和假定机制的异质性疾病。一些观察表明，慢性疲劳综合征、免疫失调、自身免疫紊乱(AID)和癌症风险增加，特别是非霍奇金淋巴瘤(NHL)之间存在关联。我们设计了一项分子流行病学调查，以探索遗传易感性和特定免疫因素在CFS病因学中的作用。我们还将研究CFS和AID之间的联系，以及CFS和癌症风险之间的潜在联系，特别是在这一人群中，NHL的风险。我们研究中的病例将从内华达州的塞拉内科诊所因感染性疾病而被诊断为急性发作的CFS病例池中确定。健康(即没有慢性阻塞性肺病、艾滋病或癌症的个人病史)无关的对照已被确定，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，并将与之接触，以参与拟议的研究。此外，我们会找出CFS病例的健康(即没有慢性疲劳综合征、艾滋病或癌症病史)的一级或二级亲属(每宗个案最少有一名亲属)，并按年龄、性别、种族和地理地区与个案配对，以与个案和对照病例比较与病毒重新激活有关的免疫学因素。一名接受过遗传咨询培训的研究助理将通过结构化电话访谈，获得所有参与者的完整家庭健康史以及流行病学和医学信息。将就自身免疫性疾病和特定类型的癌症(如非霍奇金淋巴瘤)在其亲属中的患病率对病例和对照进行比较。将从所有受试者(病例、病例亲属和对照)中获取生物样本，以比较针对EB病毒(EBV)编码蛋白的抗体水平，即EBV编码的脱氧尿苷三磷酸核苷酸水解酶(dUTP-ASE)和DNA聚合酶。本研究有可能通过研究CFS与AID家族成员之间潜在的遗传和免疫学联系，为CFS的病因和CFS是否为AID提供线索。此外，我们的研究可能为深入了解CFS和NHL之间的联系提供依据。我们的研究对公众健康的影响源于它有可能通过了解CFS、AID和NHL的病因学联系以及遗传和免疫因素的作用来早期诊断和/或治疗这些疾病。

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.