Decreased T cell precursor frequencies to Epstein-Barr virus glycoprotein gp110 in peripheral blood correlate with disease activity and severity in patients with rheumatoid arthritis

Objectives-Rheumatoid arthritis (RA) is a chronic joint disease associated with certain HLA-DR alleles expressing the QK/RRAA motif or shared epitope. The Epstein-Barr virus (EBV) has been suspected to be a causative factor f or RA. The EBV gp110, a glycoprotein of the replicative cycle that contains a copy of the shared epitope, constitutes an important target in the immun e control of EBV replication. This study evaluated the specific T cell resp onse to EBV gp110 in patients with RA expressing or not the shared epitope and examined whether this immune cellular response might be related to dise ase activity and severity. Methods-25 patients with RA were studied and compared with 25 healthy contr ols. Disease activity was assessed by biochemical markers of inflammation ( erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels), Disease severity was defined by extraarticular disease (vasculitis, subcuta neous nodules, or other organ disease). The frequencies of peripheral blood T cells specific for EBV gp110 and a control protein (total protein extrac t from Escherichia coli) were determined by direct limiting dilution analys is without preliminary bulk culture. Results-The gp110 precursor frequencies ranged from 0 to 20 x 10(-6) in pat ients with RA and controls. The mean gp110 T cell precursor frequency was l ower in patients with RA (SD 3.2 (4.4) x 10(-6)) than in healthy controls ( 4.1 (3.8) x 10(-6)) (p = 0.02). No difference was found for the control pro tein (p = 0.09). Both shared epitope positive and negative patients with RA responded to gp110, without significant difference. A negative correlation between both ESR and CRP levels and the gp110 T cell response was found (r = -0.71, p < 0.0001 and r = -0.42, p 0.038, respectively). Finally, patien ts with extra-articular disease displayed the lowest immune cellular respon se to EBV gp110. Conclusion-These results suggest that patients with RA have a decreased T c ell response to EBV gp110. Since gp110 is an important protein in the contr ol of EBV replication, this might lead to a poor control of EBV infection, chronic exposure to other EBV antigens, and thus to a chronic inflammatory response in patients with RA.