Methotrexate, a treatment for rheumatoid arthritis and polymyositis, may promote the development of Epstein-Barr virus (EBV)-positive lymphomas in patients with autoimmune diseases by reactivating latent EBV and by the drug’s immunosuppressive properties, according to a new study.

EBV is a human herpesvirus that is found in more than 90% of the adult population. The virus establishes a lifelong persistent infection of B cells and is associated with a variety of B-cell disorders, including mononucleosis and Hodgkin lymphoma. EBV-positive lymphomas occur more frequently in rheumatoid arthritis and polymyositis patients taking the drug methotrexate than in patients treated with other equally immunosuppressive drugs.

By studying the effect of methotrexate on EBV-infected cell lines, Shannon Kenney, M.D. of the Lineberger Comprehensive Cancer Center at the University of North Carolina Chapel Hill, and colleagues demonstrate that methotrexate induces reactivation of EBV from latent infection, leading to the release of infectious virions. The researchers also found that rheumatoid arthritis and polymyositis patients treated with methotrexate had higher EBV loads than patients treated with other immunosuppressive regimens. They conclude that the combination of methotrexate’s ability to induce EBV replication in such patients while promoting immunosuppression might explain the association of the drug with EBV-positive lymphomas.

Contact: Dianne Shaw, Lineberger Comprehensive Cancer Center, 919-966-5905, dgs@med.unc.edu

Contact: Sarah L. Zielinski
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Journal of the National Cancer Institute

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