Epstein–Barr virus load follow up in rheumatoid arthritis patients treated with TNF-α inhibitors

Background

In patients with rheumatoid arthritis (RA), inflammation, dysregulated Epstein–Barr virus (EBV) infection and immunosuppressive therapy may contribute to increased risk for developing lymphoma. We have shown that EBV load in peripheral blood mononuclear cells (PBLs) is 10-fold higher in RA patients (16 copies/500 ng DNA) than in normal controls (1.9 copies/500 ng DNA). EBV load in RA patients is similar to that in healthy transplant recipients and much lower than in symptomatic EBV-infected transplant recipients with lymphoproliferative disease (> 500 copies/500 ng DNA).

Objectives

We monitored EBV load in RA patients' PBLs to evaluate how it was influenced by methotrexate and infliximab, and to detect lymphoma development.

Methods

A total of 221 patients fulfilling the 1987 ACR criteria for RA and 100 healthy controls were studied. Of these 221 patients, 88 were followed for 1–4 years: 19 received only methotrexate (eight were included in the study before introduction of methotrexate), eight received only infliximab, and 61 received both methotrexate and infliximab. A 214 base-pair fragment from the EBV genome first internal repeat (IR1) was amplified by quantitative real-time PCR to evaluate EBV DNA load.

Results

EBV load decreased dramatically in most patients right after introduction of methotrexate and kept decreasing thereafter. In patients receiving infliximab and methotrexate, three patterns of EBV load evolution were observed: stable, decreasing and variable. Patients with only infliximab had either stable or decreasing EBV loads. Although an increase in EBV load was observed in a few patients, none of them reached the 500 copies/500 ng level and no patient developed lymphoma.

Conclusions

Methotrexate and infliximab do not seem to increase EBV load in patients with RA.