IDIOTYPES OF RHEUMATOID FACTORS

乔治·莫克斯利1976年在华盛顿大学获得医学博士学位， 圣路易斯。在住院医师三年和首席住院医师一年后 在内科方面，他曾是研究员，现在是助理 风湿学教授，第一个有一年密集临床接触的人 之后，肖恩博士将进行为期五年的实验室工作 鲁迪。他已经开发了酶联免疫分析方法来鉴定单克隆性 他通过体细胞杂交产生的抗体 指向补体蛋白。他通过放射免疫分析发现 患者滑液中C3过敏性毒素显著升高 患有类风湿性关节炎(RA)和急性痛风性关节炎。假说 在这项提案中要检查的是，RA患者会产生类风湿 与疾病相关的交叉反应独特型的因子(RF)和 与RF阳性的疾病患者的免疫球蛋白不同 而不是RA。在分析方面已经取得了实质性进展。 申请人已经开发出制备单电池的技术 类风湿滑膜组织淋巴细胞的悬液，转化B EB病毒感染的淋巴细胞，并分析培养上清液 人类免疫球蛋白或RFS。他已经制造出了针对一种 代表单克隆性RF的重要组成部分的合成肽。他 已经合成了与RF重要部分互补的寡核苷酸 轻链基因，并利用它们与南方杂交 类风湿性关节炎(RA)患者或正常人。拟议的研究 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 患有类风湿关节炎以外疾病的RF阳性患者 与人工合成的寡核苷酸的杂交；以及其一级结构 免疫球蛋白将在类风湿滑液或血清中进行比较 用抗肽免疫印迹法检测缺乏RA的RF阳性个体 抗血清。

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.