Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment.
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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.
Antibodies, Monoclonal, Humanized
Lymphocyte Culture Test, Mixed
Mice, Inbred C57BL
Published Version (Please cite this version)10.1111/j.1600-6143.2012.04181.x
Publication InfoBulut, OP; Farris, AB; Gibby, Adriana C; Iwakoshi, Neal N; Kim, DW; Kirk, Allan D; ... Song, MQ (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 http://hdl.handle.net/10161/10058.
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William R. Kenan, Jr. Professor
During my career as an academic surgeon, I have had the privilege of leading and/or participating in a diverse portfolio of hypothesis-driven research projects. These projects have centered on the immunology of surgery and transplantation, including both cellular and antibody-mediated immune responses. During my training I studied the response of hyper-sensitized recipients to allogeneic liver transplantation, and am currently studying means of reducing immunologic memory that might
Assistant Professor of 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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