This proposal will extend work in three main areas: 1) pathogenesis of acute rheumatic fever and its possible relationship to B-cell alloantigens defined by two recently-developed mouse monoclonal antibodies 883 and 256; 2) studies of antiidiotypic control mechanisms influencing anti-ds-DNA antibody production during the course of systemic lupus erythematosus (SLE); and 3) further investigations concerning immunochemical specificity and possible physiologic significance of anti-lymphocyte antibodies in patients with SLE. The work directed at possible B-cell alloantigen control of host immune response to group A streptococcal antigens will attempt to provide better immunochemical definition of the B-cell surface components reacting with the 883 and 256 reagents. In addition, comparative in vitro assays are planned using various streptococcal and control antigens in experiments using peripheral blood and mononuclear cell stimulation and macrophage pulsing with 883/256 (+) and (-) donors. Studies of anti-idiotypic control mechanisms in SLE will utilize monoclonal murine antibodies produced against a panel of isolated SLE anti-ds-DNA antibodies as well as radioimmunoassay and ELISA techniques to define auto-anti-DNA idiotypic reactions. The possibility that antibodies showing anti-F(ab')2 specificity may be representative of a broad pool of anti-idiotypes some of which are enriched for antids-DNA anti-idiotypic reactivity will be sequentially explored using affinity column purified anti-DNA and anti-F(ab')2 antibodies and ELISA assay techniques. Finally, specific studies of lymphocyte glycoproteins reacting with anti-lymphocyte antibodies from SLE will be performed using lymphocyte cell membrane proteins separated by SDS PAGE gels and transferred to nitrocellulose paper. Further definition of the mechanisms whereby IgG antibodies from SLE serum are capable of penetrating living cells will be performed using sequential electronmicroscope monitoring.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR013690-19
Application #
3154775
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1976-05-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
19
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of New Mexico
Department
Type
Schools of Medicine
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Williams Jr, R C (1992) Rheumatoid factors: historical perspective, origins and possible role in disease. J Rheumatol Suppl 32:42-5
Yancey Jr, W B; Silvestris, F; Conlon, M et al. (1992) Human anti-F(ab')2 antibodies show preferential reactivity for F(ab')2 molecules bearing lambda light chains. Clin Immunol Immunopathol 65:176-82
Silvestris, F; Rots, N; Yancey Jr, W B et al. (1991) Monoclonal antibodies against human anti-F(ab')2 antibodies react with light chain epitopes. Clin Immunol Immunopathol 59:139-55
Silvestris, F; Yancey Jr, W B; Malone, C et al. (1991) Parallelism of serum anti-F(ab')2 and anti-cationic IgG reactivities in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 59:256-70
Husby, G; Tsuchiya, N; Schwimmbeck, P L et al. (1989) Cross-reactive epitope with Klebsiella pneumoniae nitrogenase in articular tissue of HLA-B27+ patients with ankylosing spondylitis. Arthritis Rheum 32:437-45
Silvestris, F; Searles, R A; Capra, J D et al. (1989) Studies of anti-F(ab')2 antibodies and VH region distribution among SLE kindreds. J Autoimmun 2:395-401
Silvestris, F; Searles, R A; Williams Jr, R C et al. (1989) Distribution of anti-F(ab')2 antibodies and the 16/6 idiotype in systemic lupus erythematosus (SLE) probands and kindreds. J Clin Immunol 9:462-8