Over the past two decades numerous studies have demonstrated that a chronic relapsing remitting model of arthritis in rats can be induced following a single injection of streptococcal cell walls. Cardinal features of this model, many of which are similar to the human disease, are 1) the relapsing remitting nature of the arthritis 2) a genetic female predisposition 3) T-cell dependency of the model 4) cellular infiltrates in the synovia of the affected joints 5) restriction to the distral joints (paws) of the animal 6) persistence of the antigen in the affected tissues 7) expression of Ia antigen in the cells and tissues of the affected area. In spite of these elegant experiments we still know very little concerning the exact nature and structural properties of the inducing antigen and how it produces disease. Thus we plan to carry out the following experiments. 1) Pursuit of the minimal size of the inducing antigen and whether it might require carrier proteins for full expression of the chronic disease. 2) To determine what are the biochemical features of the antigen that are important for inducing the model. 3) To determine what lymphokines are important in inducing the expression of the model. 4) To explore the question of whether or not a newly described M protein moiety """"""""buried"""""""" in the streptococcal cell wall complex which exhibits a high degree of homology with various collagens plays a important role in this rat arthritis model. 5) Finally, to determine whether there is a difference in the cellular reactivity to the more purified cell wall material and/or the M protein moiety in Rheumatic Arthritis patients compared to controls. Hopefully further information gained from this animal model and a few selected studies in humans will shed light on the pathogenetic mechanisms involved in the human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR039037-01
Application #
3159088
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065