Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients.
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.
Keymeulen
Bart
B
Academisch Ziekenhuis and Diabetes Research Center, Brussels Free University-VUB, Brussels, Belgium.
Candon
Sophie
S
Fafi-Kremer
Samira
S
Ziegler
Anette
A
Leruez-Ville
Marianne
M
Mathieu
Chantal
C
Vandemeulebroucke
Evy
E
Walter
Markus
M
Crenier
Laurent
L
Thervet
Eric
E
Legendre
Christophe
C
Pierard
Denis
D
Hale
Geoff
G
Waldmann
Herman
H
Bach
Jean-François
JF
Seigneurin
Jean Marie
JM
Pipeleers
Daniel
D
Chatenoud
Lucienne
L
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
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004279:DNA, Viral; D010919:Placebos