As the etiology of rheumatoid arthritis is still obscure despite its widespread prevalence, a system to study rheumatoid factro, cross-reactive idiotypic expression offers insight into this disease. Rheumatoid factors have been imiplicated as mediators in synovial tissue destruction. Their role as to cause or effect in the disease process is still obscure. The demonstration of a strong similarity among rheumatoid factors, monoclonal IgM proteins' specific antigenic determinants (idiotypes), from patients with Waldenstroms' macroglobulinaemia, suggests a system to study the expression of this rheumatoid factor cross-reactive idiotype in a polyclonal disease, namely rheumatoid arthritis. We have already demonstrated a marked increase in the expression of rheumatoid cross-reactive idiotype (RCRI), positive plasma cells induced by pokeweek mitogen in patients with rheumatoid arthritis (11-21% of total plasma cells derived from peripheral blood lymphoclytes) as compared to 1-3% in normal controls. We plan to extend our series of rheumatoid patients to include those whose sera are negativefor rheumatoid factor but possess the clinical disease. Monomeric IgM found in the sera and synovial fluid of some patients with rheumatoid arthritis will be examined for the presence of the RCRI despite their inability to bind aggregated human IgG, possibly because of decreased avidity of the monomer as opposed to the pentamer. The T cell compartment in rheumatoid patients will be assayed in vitro with normal B cells to question its role in inducing the increased expression of RCRI in PWM cultures. Finally an attempt to produce a monoclonal anti-RCRI reagent to study the idiotype expression in pokeweed induced plasma cells from patients with seropositive and negative rehumatoid arthritis will be pursued to obtain a standardized reagent possibly useful as a definite assay for some rheumatoid factors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR031936-05
Application #
3156152
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-08-01
Project End
1988-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027