Increased frequency of T cells specific for EBV gp110 in the synovial fluid of patients with rheumatoid arthritis

Background

The shared epitope (SE) helps the development of rheumatoid arthritis (RA) by an unknown mechanism. The Epstein–Barr virus (EBV) glycoprotein gp110, a major target in the immune control of EBV replication, contains a copy of the SE. We previously showed that frequencies of T-cell precursors specific to EBV gp110 are influenced by HLA-DR polymorphism and that RA patients have low frequencies of T cells specific for EBV gp110.

Objective

To determine the frequency of T cells (limiting dilution analysis) specific for EBV gp110 and a control antigen (Escherichia coli protein extract) in the synovial fluid of patients with RA or various forms of arthritis.

Methods

Nine RA patients (ACR 1987 criteria; mean age 61.1 ± 7.3 years) and 10 controls with inflammatory rheumatic diseases (mean age 42.5 ± 17.4 years) were studied. For RA patients, the frequency of both peripheral blood and synovial T cells specific for EBV gp110 was evaluated.

Results

In the synovial fluid, the frequency of T cells specific for EBV gp110 was significantly higher in RA than in non-RA patients (mean ± SD 2.5 ± 1.6 × 10^-6 vs 0.7 ± 0.9 × 10^-6; P = 0.02) (no difference for the control antigen: 1.9 ± 3.3 × 10^-6 vs 2.1 ± 2.0 × 10^-6; P = 0.3). In RA patients, the frequency of T cells proliferating to gp110 was higher in the synovial fluid than in peripheral blood, but without achieving statistical significance (2.5 ± 1.6 × 10^-6 vs 2.0 ± 1.8 × 10^-6; P = 0.7) (no difference for the control antigen).

Conclusion

A high frequency of T cells specific for EBV gp110 can be detected in the synovial fluid of RA patients, providing further support for the argument that EBV is involved in RA pathogenesis.