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
- aDepartment of Rheumatology, University Hospital J Minjoz, Bd A Fleming, 25030 F-Besançon, France, bImmunogenetic Laboratory, Blood Transfusion Centre, 25000 F-Besançon, France, cEastern Virginia Medical School, Department of Pathology, Norfolk, Virginia, USA, dImmunorheumatology, INSERM E9940 Université de la Méditerranée, F-13005 Marseille, France
- Dr E Toussirot, Department of Rheumatology, University Hospital J Minjoz, Bd A Fleming, 25030 F-Besançon, France Email:
- Accepted 17 January 2000
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 for RA. The EBV gp110, a glycoprotein of the replicative cycle that contains a copy of the shared epitope, constitutes an important target in the immune control of EBV replication. This study evaluated the specific T cell response to EBV gp110 in patients with RA expressing or not the shared epitope and examined whether this immune cellular response might be related to disease activity and severity.
METHODS 25 patients with RA were studied and compared with 25 healthy controls. Disease activity was assessed by biochemical markers of inflammation (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels). Disease severity was defined by extra-articular disease (vasculitis, subcutaneous nodules, or other organ disease). The frequencies of peripheral blood T cells specific for EBV gp110 and a control protein (total protein extract fromEscherichia coli) were determined by direct limiting dilution analysis without preliminary bulk culture.
RESULTS The gp110 precursor frequencies ranged from 0 to 20 × 10−6in patients with RA and controls. The mean gp110 T cell precursor frequency was lower in patients with RA (SD 3.2 (4.4) × 10-6) than in healthy controls (4.1 (3.8) × 10-6) (p = 0.02). No difference was found for the control protein (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, patients with extra-articular disease displayed the lowest immune cellular response to EBV gp110.
CONCLUSION These results suggest that patients with RA have a decreased T cell response to EBV gp110. Since gp110 is an important protein in the control 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.
- T cell precursor frequency
- Epstein-Barr virus
- glycoprotein gp110
- rheumatoid arthritis
- disease severity