AUTOANTIBODIES TO CELLULAR MATRIX ANTIGENS IN CFS

CFS 中细胞基质抗原的自身抗体

• 批准号: 2887403
• 负责人: Eng M TAN
• 金额: $ 34.48万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-15 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887403
• 关键词: Sjogren's syndrome; autoantibody; blood chemistry; chronic fatigue syndrome; clinical research; clinical trials; enzyme linked immunosorbent assay; fibromyalgia; gene expression; genetic library; human tissue; humoral immunity; immunofluorescence technique; lamins; nuclear membrane; polymerase chain reaction; radioimmunoassay; vimentin

DESCRIPTION: (Adapted from Investigator's Abstract) On the basis of recent studies it has been shown that CFS sera contain antibodies to relatively insoluble cellular matrix antigens. Cellular structures (nuclear envelope, vimentin-containing intermediate filaments and a nuclear matrix particle visualized in immunofluorescence as reticulated speckles) associated with these antigens contain proteins that are part of the nuclear or cytoplasmic matrix. In collaboration with investigators at the University of Washington and at Harvard University, the PI and co-investigators at Scripps Research Institute will examine four research aims: 1) using previously collected blood samples from CFS patients from the two CFS center clinics and using currently developed assays the blood samples will be analyzed for the antibodies. They will be compared with patients with primary Sjogren's syndrome and primary fibromyalgia to determine whether differences in autoantibody specificities exist between different diseases and between CFS patients from different clinics; 2) ELISA assays will be developed for anti-lamin B1 and anti-vimentin using recombinant proteins expressed from cDNA clones, so that differences in antibody levels could be quantitated. This would be used in longitudinal studies of CFS patients to determine the role of humoral immunity in the natural history of the illness; 3) the possibility that there might be CFS-specific epitopes on lamin B1 and vimentin will be explored with expression products of PCR constructs, because if CFS-specific epitopes are detected, synthetic peptides of these regions could be used in highly specific immunological assays; 4) antibody screening of cDNA expression libraries will be performed to isolate the reticulated speckles nuclear antigen and a 45 kDa antigen. The antibody to the reticulated speckles could be a new or unique marker for CFS. The antibody to the 45 kDa antigen is present in Sjogren's syndrome but not in CFS-sicca and appears to be a distinguishing feature between the two clinical entities. Overall, these studies are aimed at rigorously defining autoantibody reactivities in CFS and may have etiologic implications.

描述：(改编自《调查者摘要》)基于最近的 研究表明，CFS血清中含有相对特异的抗体 不溶的细胞基质抗原。细胞结构(核膜， 含波形蛋白的中间丝和核基质颗粒 在免疫荧光中显示为网状斑点)与 这些抗原包含核内或细胞质中的蛋白质。 矩阵。与华盛顿大学的研究人员合作 在哈佛大学，私家侦探和斯克里普斯研究公司的联合调查员 研究所将检查四个研究目标：1)使用以前收集的 从两个CFS中心诊所采集CFS患者的血液样本，并使用 目前开发的血样分析方法将用于分析 抗体。他们将与原发性干燥症患者进行比较。 辨证分型与原发性纤维肌痛是否存在差异 自身抗体在不同疾病之间和CFS之间存在特异性 来自不同诊所的患者；2)将开发用于 利用重组蛋白表达抗层粘连蛋白B1和抗波形蛋白 C DNA克隆，以便对抗体水平的差异进行定量。 这将被用于对CFS患者的纵向研究，以确定 体液免疫在疾病自然病程中的作用；3) 可能在Lamin B1和Lamin B1上存在CFS特异性表位 将用PCR构建体的表达产物来探索波形蛋白， 因为如果检测到CFS特异性表位，这些合成肽 区域可用于高度特异的免疫学分析；4)抗体 将进行cDNA表达文库的筛选，以分离出 网状斑点核抗原和一个45 kDa的抗原。抗病毒抗体 网状散斑可能是CFS的一个新的或唯一的标志物。这个 干燥综合征患者中存在45 kDa抗原抗体，而干燥综合征患者中不存在 CFS-SICCA，似乎是两者的一个区别特征 临床实体。总体而言，这些研究的目的是严格定义 CFS中自身抗体的反应性，可能具有病因学意义。