Search for correlation of CD8 T cell response to Epstein-Barr virus with clinical status in rheumatoid arthritis: a 15 month followup pilot study.

Objective: To assess in a longitudinal 15 month followup study the CD8 T cell response to immunodominant Epstein-Barr virus (EBV) antigens of 17 patients with rheumatoid arthritis (RA); and to seek an association between these responses and both clinical activity/severity of RA and a qualitative PCR for EBV in peripheral blood.

Methods: At each patient's visit every 3 months: (1) RA activity was assessed for Disease Activity Score (DAS-28); (2) a qualitative PCR for EBV was performed; (3) CD8 T cell response to EBV epitopes was screened in peripheral blood, using an autopresentation assay of 13 EBV peptides previously identified as immunodominant targets in RA synovia. Activation of anti-EBV CD8 T cells was evaluated by measuring the release of tumor necrosis factor-a.

Results: The semiquantitative CD8 T cell response to EBV roughly paralleled RA clinical activity in only 4/17 patients. No clear association could be found between positive PCR for EBV (performed at least once in 10/17 patients) and RA activity/severity or fatigue. Reactivity was not qualitatively broader in samples where PCR for EBV proved positive, and most often focused on one or 2 EBV antigens. However, these antigens differed between patients, as did the magnitude of CD8 T cell response to immunodominant antigens at different timepoints for the same patient.

Conclusion: The CD8 T cell response to EBV paralleled clinical activity in only 4/17 patients. Our pilot study does not support the hypothesis that this CD8 response contributes to RA activity/flares, although the quantitative variations in the pattern of this reactivity over time confirmed that control of EBV manifestations was difficult in most patients with RA.