IDIOTYPES OF RHEUMATOID FACTORS

类风湿因子的独特型

• 批准号: 3456754
• 负责人: GEORGE F MOXLEY
• 金额: $ 9.18万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/3456754
• 关键词: B lymphocyte; antigen antibody reaction; antigens; autoantibody; autoimmune disorder; cross immunity; enzyme linked immunosorbent assay; gel electrophoresis; human subject; immune complex; immunoglobulin genes; immunoglobulin idiotypes; immunoglobulin structure; leukocyte activation /transformation; molecular pathology; monoclonal antibody; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; rheumatoid arthritis; rheumatoid factor; synovial fluid; synthetic nucleic acid; synthetic peptide; tissue /cell culture

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·莫斯利于1976年获得华盛顿大学的医学博士学位，