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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.

Original publication

DOI

10.1182/blood-2009-02-204875

Type

Journal article

Journal

Blood

Publication Date

11/02/2010

Volume

115

Pages

1145 - 1155

Keywords

Antibodies, Monoclonal, Antigens, CD3, B-Lymphocytes, DNA, Viral, Diabetes Mellitus, Type 1, Epstein-Barr Virus Infections, Flow Cytometry, Graft Survival, Herpesvirus 4, Human, Humans, Kidney Transplantation, Palatine Tonsil, Phenotype, Placebos, Polymerase Chain Reaction, T-Lymphocytes, Viral Load, Virus Activation