Transient Epstein Barr virus reactivation in CD3 monoclonal antibody-treated patients
Keymeulen, Bart * Candon, Sophie * Fafi-Kremer, Samira Ziegler, Anette Leruez-Ville, Marianne Mathieu, Chantal Vandemeulebroucke, Evy Walter, Markus Crenier, Laurent Thervet, Eric Legendre, Christophe Pierard, Denis Hale, Geoff Waldmann, Herman Bach, Jean-Francois Seigneurin, Jean Marie Pipeleers, Daniel Chatenoud, Lucienne # ×
Blood vol:115 issue:6 pages:1145-1155
Here we report a unique situation in which an early and synchronized EBV reactivation was induced by a 6-day course treatment with a humanized CD3-specific monoclonal antibody in patients with recent onset of type 1 diabetes. The virological and immunological analysis showed 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 was associated with induced short lasting immunosuppression and minor yet clear-cut signs of T cell activation that preceded viral reactivation. Early post-transplant monitoring of renal and islet allograft recipients showed that no comparable phenomenon was observed following 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.