Epstein-Barr Virus (EBV) Prevalence and the Risk of Reactivation in Patients with Inflammatory Arthritis Using Anti-TNF Agents and in those who are Biologic Naive

Emily McKeown1, Janet E Pope*, 2, Suzanne Leaf2
1 Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
2 Division of Rheumatology, St. Joseph’s Health Centre, London, Ontario, Canada

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© McKeown et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Division of Rheumatology, St. Joseph’s Health Centre, 268 Grosvenor St., London, ON N6A 4V2, Canada; Tel: 519-646-6332; Fax: 519-646-6334; E-mail:



Anti-TNF agents (etanercept, infliximab and adalimumab) are widely used in inflammatory conditions, such as rheumatoid arthritis; however, they are not without side effects, potentially including lymphoma. We compared Epstein-Barr virus (EBV) levels in patients with inflammatory arthritis taking biologic agents and controls matched for disease, age, gender and disease duration who were biologic naïve. Secondly, we determined the risk of reactivation of EBV in patients taking biologics.


One hundred and twenty-two patients were recruited and blood samples were collected. Immunoglobulin G (IgG) antibody to EBV was analysed using enzyme-linked immunosorbent assay. EBV DNA was analysed using polymerase chain reaction (PCR) on all positive IgG samples. Quantitative measures of viral DNA were made and expressed as copies/reaction volume. Reactivation was defined as the presence of viral DNA in the plasma and PCR activity was evaluated between 6 and 18 months after anti-TNF therapy.


IgG for EBV was detected in 98% of controls and 90% of cases. Viral reactivation related to EBV was not observed in this study. There was one patient who tested positive for EBV using PCR, but upon confirmatory testing, this sample was actually negative. No samples were positive on PCR at the follow-up time points.


There was a high rate of EBV IgG in the cases and controls in this study. Given the small sample size and timeframe for this study, treatment with anti-TNF agents does not seem to lead to EBV reactivation, and thus, this is likely not a mechanism for the development of lymphoma in patients taking biologics.

Keywords:: Rheumatoid arthritis, anti-TNF therapy, reactivation, Epstein-Barr Virus, lymphoma..