Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients.
Keymeulen B., Candon S., Fafi-Kremer S., Ziegler A., Leruez-Ville M., Mathieu C., Vandemeulebroucke E., Walter M., Crenier L., Thervet E., Legendre C., Pierard D., Hale G., Waldmann H., Bach JF., Seigneurin JM., Pipeleers D., Chatenoud L.
Here we report a unique situation in which an early and synchronized Epstein-Barr virus (EBV) reactivation was induced by a 6-day course of treatment with a humanized CD3-specific monoclonal antibody in patients with recent onset of type 1 diabetes. The virologic and immunologic analysis demonstrated that this reactivation was transient, self-limited, and isolated, associated with the rapid advent of an EBV-specific T-cell response. The anti-CD3 antibody administration induced short-lasting immunosuppression and minor yet clear-cut signs of T-cell activation that preceded viral reactivation. Early posttransplant monitoring of renal and islet allograft recipients showed that no comparable phenomenon was observed after the administration of full-dose immunosuppressive therapy. This EBV reactivation remains of no apparent clinical concern over the long term and should not preclude further development of therapeutic anti-CD3 antibodies. This phenomenon may also direct new research avenues to understand the still ill-defined nature of stimuli triggering EBV reactivation in vivo.