Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment.
Abstract
Even though the etiology of chronic rejection (CR) is multifactorial, donor specific
antibody (DSA) is considered to have a causal effect on CR development. Currently
the antibody-mediated mechanisms during CR are poorly understood due to lack of proper
animal models and tools. In a clinical setting, we previously demonstrated that induction
therapy by lymphocyte depletion, using alemtuzumab (anti-human CD52), is associated
with an increased incidence of serum alloantibody, C4d deposition and antibody-mediated
rejection in human patients. In this study, the effects of T cell depletion in the
development of antibody-mediated rejection were examined using human CD52 transgenic
(CD52Tg) mice treated with alemtuzumab. Fully mismatched cardiac allografts were transplanted
into alemtuzumab treated CD52Tg mice and showed no acute rejection while untreated
recipients acutely rejected their grafts. However, approximately half of long-term
recipients showed increased degree of vasculopathy, fibrosis and perivascular C3d
depositions at posttransplant day 100. The development of CR correlated with DSA and
C3d deposition in the graft. Using novel tracking tools to monitor donor-specific
B cells, alloreactive B cells were shown to increase in accordance with DSA detection.
The current animal model could provide a means of testing strategies to understand
mechanisms and developing therapeutic approaches to prevent chronic rejection.
Type
Journal articleSubject
AnimalsAntibodies, Monoclonal, Humanized
Antibody Formation
B-Lymphocytes
Chronic Disease
Flow Cytometry
Graft Rejection
Heart Transplantation
Immunohistochemistry
Isoantibodies
Lymphocyte Culture Test, Mixed
Mice
Mice, Inbred C57BL
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https://hdl.handle.net/10161/10058Published Version (Please cite this version)
10.1111/j.1600-6143.2012.04181.xPublication Info
Kwun, J; Oh, BC; Gibby, AC; Ruhil, R; Lu, VT; Kim, DW; ... et al. (2012). Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft
rejection after alemtuzumab treatment. Am J Transplant, 12(10). pp. 2641-2651. 10.1111/j.1600-6143.2012.04181.x. Retrieved from https://hdl.handle.net/10161/10058.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Jean Kwun
Associate Professor in Surgery
Research interests include humoral tolerance to organ transplants in animal model
and humans, developing a clinically relevant animal model to study the mechanisms
of antibody-mediated rejection (AMR), and establishing a conceptual basis that will
translate into therapeutic intervention of AMR.

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