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AUTOANTIBODIES TO CELLULAR MATRIX ANTIGENS IN CFS

CFS 中细胞基质抗原的自身抗体

基本信息

批准号：
6170028
负责人：
Eng M TAN
金额：
$ 31.72万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-05-15 至 2002-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6170028
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

项目摘要

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：（改编自研究者摘要）根据最近的研究表明，CFS血清含有相对不溶性细胞基质抗原。细胞结构（核膜，含有波形蛋白的中间丝和核基质颗粒在免疫荧光中可视化为网状斑点），这些抗原含有属于细胞核或细胞质的蛋白质矩阵与华盛顿大学的研究人员合作，在哈佛大学，PI和Scripps Research的合作研究人员研究所将审查四个研究目标：1）使用以前收集的来自两个CFS中心诊所的CFS患者的血液样本，目前开发的测定法，血液样品将被分析用于抗体的他们将与原发性干燥综合征患者进行比较综合征和原发性纤维肌痛，以确定是否差异，不同疾病之间和CFS之间存在自身抗体特异性来自不同诊所的患者; 2）将开发ELISA测定法，抗核纤层蛋白B1和抗波形蛋白， cDNA克隆，以便可以定量抗体水平的差异。这将用于CFS患者的纵向研究，以确定体液免疫在疾病自然史中的作用; 3）核纤层蛋白B1上可能存在CFS特异性表位，将用PCR构建体的表达产物研究波形蛋白，因为如果检测到CFS特异性表位，可用于高特异性的免疫学检测; 4）抗体将进行cDNA表达文库的筛选以分离网状斑点核抗原和45 kDa抗原。抗体与网状斑点可能是CFS的一个新的或独特的标记。的抗45 kDa抗原的抗体存在于干燥综合征中，但不存在于 CFS-sicca和似乎是两者之间的区别特征临床实体总的来说，这些研究旨在严格定义 CFS中的自身抗体反应性，并可能具有病因学意义。