Fibrinogen-specific T cells in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by the occurence of autoreactive antibodies and T cells. The family of antibodies directed to citrulline-containing antigens (anti-filaggrin, anti-CCP and anti-Sa) have the highest specificity (>98%) for RA. To investigate the presence of citrulline-specific T cells in RA patients, we analyzed T-cell reactivity to unmodified and citrullinated filaggrin and fibrinogen in modified T-cell proliferation assays. No T-cell responses were observed when either unmodified or citrullinated filaggrin was used as the stimulating antigen in serum-free T-cell proliferation assays. With unmodified fibrinogen, however, T-cell proliferation was observed in 8/15 (53%) of RA patients, while only 1/14 control patients (SLE, SSc, PsoA, Sjö) displayed clearly positive T-cell proliferation. The difference was highly significant (P < 0.0001). These findings were even more pronounced when using citrullinated fibrinogen as stimulating antigen: 10/15 (67%) RA patients were positive for T-cell proliferation and again only 1/14 control patients was clearly positive (P < 0.0001). T-cell reactivity in RA patients was significantly (P < 0.05) higher against citrullinated as compared with unmodified fibrinogen.

We conclude that fibrinogen (citrullinated or not) can induce proliferation of RA T cells, thereby further substantiating its pathogenic relevance.