title: Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients.
abstract: 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.
authors.affiliation: Academisch Ziekenhuis and Diabetes Research Center, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
authors.forename: Sophie
authors.initials: S
authors.lastname: Candon
authors.forename: Samira
authors.initials: S
authors.lastname: Fafi-Kremer
authors.forename: Anette
authors.initials: A
authors.lastname: Ziegler
authors.forename: Marianne
authors.initials: M
authors.lastname: Leruez-Ville
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: Evy
authors.initials: E
authors.lastname: Vandemeulebroucke
authors.forename: Markus
authors.initials: M
authors.lastname: Walter
authors.forename: Laurent
authors.initials: L
authors.lastname: Crenier
authors.forename: Eric
authors.initials: E
authors.lastname: Thervet
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Denis
authors.initials: D
authors.lastname: Pierard
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bach
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Seigneurin
authors.forename: Daniel
authors.initials: D
authors.lastname: Pipeleers
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D016030:Kidney Transplantation; D014066:Palatine Tonsil / Q000166:cytology; D010641:Phenotype; D010919:Placebos; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D014775:Virus Activation
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004279:DNA, Viral; D010919:Placebos