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IDIOTYPES OF RHEUMATOID FACTORS

类风湿因子的独特型

基本信息

批准号：
3456756
负责人：
GEORGE F MOXLEY
金额：
$ 9.36万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-08-01 至 1991-07-31
项目状态：
已结题

项目摘要

George Moxley received the MD degree in 1976 from Washington University, St. Louis. After three years of residency and one year of chief residency in internal medicine, he has trained as a fellow and now as an assistant professor of rheumatology, first with a year of intensive clinical exposure followed by what will be five years of laboratory work with Dr. Shaun Ruddy. He has developed enzyme-linked immunoassays to identify monoclonal antibodies which he has produced by somatic cell hybridization and that are directed toward complement proteins. He has found by radioimmunoassay striking elevations of C3 anaphylatoxins in synovial fluids of patients with rheumatoid arthritis (RA) and acute gouty arthritis. The hypothesis to be examined in this proposal is that patients with RA produce rheumatoid factors (RFs) with cross-reactive idiotypes which are disease related and distinct from such immunoglobulins in RF-positive individuals with diseases other than RA. Substantial progress has been made toward the analysis. The applicant has developed techniques for preparing single cell suspensions of lymphocytes from rheumatoid synovial tissue, transforming B lymphocytes with Epstein-Barr virus, and analyzing culture supernatants for human immunoglobulin or RFs. He has produced antisera directed toward a synthetic peptide representing an important part of a monoclonal RF. He has synthesized oligonucleotides complementary to important parts of RF light chain genes and used them for hybridization to Southern blots of patients with rheumatoid arthritis (RA) or normals. The proposed research will compare immunoglobulin genes among rheumatoid synovium and cells of RF-positive individuals with diseases other than RA by means of hybridization with synthetic oligonucleotides; and the primary structure of immunoglobulins will be compared among rheumatoid synovial fluids or sera of RF-positive individuals lacking RA by immunoblotting with an antipeptide antiserum.

乔治莫克斯利于1976年获得华盛顿大学的医学博士学位，圣Louis. 在做了三年的住院医师和一年的总住院医师之后在内科学方面，他曾接受研究员培训，现在是助理风湿病学教授，第一次与一年的密集临床接触接下来是肖恩博士五年的实验室工作好红他开发了酶联免疫测定法，他通过体细胞杂交产生的抗体，针对补体蛋白质。他通过放射免疫分析发现患者滑液中C3过敏毒素显着升高类风湿性关节炎（RA）和急性痛风性关节炎。的假设在这个建议中要检查的是，RA患者产生类风湿性关节炎，与疾病相关的交叉反应独特型因子（RF），与患有疾病的RF阳性个体中的此类免疫球蛋白不同除了RA。分析工作取得了重大进展。申请人开发了制备单细胞的技术，来自类风湿性滑膜组织的淋巴细胞悬液，转化B 用EB病毒感染淋巴细胞，并分析培养上清液中的人免疫球蛋白或RF。他已经生产出了针对代表单克隆RF的重要部分的合成肽。他已经合成了与RF的重要部分互补的寡核苷酸，轻链基因，并将其用于杂交的Southern印迹，类风湿性关节炎（RA）患者或正常人。拟议研究将比较类风湿滑膜和类风湿关节炎细胞中的免疫球蛋白基因， RF阳性个体患有除RA以外的疾病，与合成的寡核苷酸杂交;以及免疫球蛋白将在类风湿关节液或血清中进行比较通过抗肽免疫印迹检测缺乏RA的RF阳性个体抗血清