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Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment.

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Accepted version
130.1 Kb
Accepted version
101.9 Mb
Date
2012-10
Authors
Kwun, J
Oh, BC
Gibby, AC
Ruhil, R
Lu, VT
Kim, DW
Page, EK
Bulut, OP
Song, MQ
et al.
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(10 total)
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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 article
Subject
Animals
Antibodies, Monoclonal, Humanized
Antibody Formation
B-Lymphocytes
Chronic Disease
Flow Cytometry
Graft Rejection
Heart Transplantation
Immunohistochemistry
Isoantibodies
Lymphocyte Culture Test, Mixed
Mice
Mice, Inbred C57BL
Permalink
https://hdl.handle.net/10161/10058
Published Version (Please cite this version)
10.1111/j.1600-6143.2012.04181.x
Publication 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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Scholars@Duke

Kwun

Jean Kwun

Assistant 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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