ENHANCED T CELL PROLIFERATIVE RESPONSE TO TYPE II COLLAGEN AND SYNTHETIC PEPTIDE CII (255–274) IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract

Objective

To determine the presence of specific immune recognition of type II collagen (CII) and its immunodominant epitope CII (255–274) in patients with rheumatoid arthritis (RA).

Methods

T cell proliferative responses to bovine CII and a synthetic peptide encompassing CII (255–274) in peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from RA patients, and in PBMC from osteoarthritis (OA) patients and healthy controls were assayed by mixed lymphocyte culture.

Results

The stimulation index (SI) and the number of positive (SI ≥2) T cell responses to CII were higher in RA patients (n = 106) than in OA patients (n = 26) and healthy controls (n = 34). T cell responses to CII (255–274) were also enhanced in RA patients and correlated well with those to CII. In SFMC, positive responses to CII or CII (255–274) were detected in 61.9% of 42 RA patients. T cell responses to CII in SFMC were stronger and more prevalent than peripheral responses. The SI and positive responses to CII were higher in early RA than in late RA. Levels of IgG antibodies to CII in synovial fluid inversely correlated with T cell responses to CII.

Conclusion

T cell responses to CII or CII (255–274) were enhanced in RA, especially in early disease. Synthetic peptide CII (255–274), as well as native CII, could be recognized as immunogenic antigens by T cells, particularly in the synovial fluid. These observations suggest that CII-reactive T cells play an important role in the pathogenesis of RA. Peripheral tolerance induction using CII (255–274) might be useful in the treatment of RA.