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

Publication ,  Journal Article
Kwun, J; Oh, BC; Gibby, AC; Ruhil, R; Lu, VT; Kim, DW; Page, EK; Bulut, OP; Song, MQ; Farris, AB; Kirk, AD; Knechtle, SJ; Iwakoshi, NN
Published in: Am J Transplant
October 2012

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.

Duke Scholars

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

October 2012

Volume

12

Issue

10

Start / End Page

2641 / 2651

Location

United States

Related Subject Headings

  • Surgery
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Culture Test, Mixed
  • Isoantibodies
  • Immunohistochemistry
  • Heart Transplantation
  • Graft Rejection
  • Flow Cytometry
  • Chronic Disease
 

Citation

APA
Chicago
ICMJE
MLA
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Kwun, J., Oh, B. C., Gibby, A. C., Ruhil, R., Lu, V. T., Kim, D. W., … Iwakoshi, N. N. (2012). Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment. Am J Transplant, 12(10), 2641–2651. https://doi.org/10.1111/j.1600-6143.2012.04181.x
Kwun, J., B. C. Oh, A. C. Gibby, R. Ruhil, V. T. Lu, D. W. Kim, E. K. Page, et al. “Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment.Am J Transplant 12, no. 10 (October 2012): 2641–51. https://doi.org/10.1111/j.1600-6143.2012.04181.x.
Kwun J, Oh BC, Gibby AC, Ruhil R, Lu VT, Kim DW, et al. Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment. Am J Transplant. 2012 Oct;12(10):2641–51.
Kwun, J., et al. “Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment.Am J Transplant, vol. 12, no. 10, Oct. 2012, pp. 2641–51. Pubmed, doi:10.1111/j.1600-6143.2012.04181.x.
Kwun J, Oh BC, Gibby AC, Ruhil R, Lu VT, Kim DW, Page EK, Bulut OP, Song MQ, Farris AB, Kirk AD, Knechtle SJ, Iwakoshi NN. Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment. Am J Transplant. 2012 Oct;12(10):2641–2651.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

October 2012

Volume

12

Issue

10

Start / End Page

2641 / 2651

Location

United States

Related Subject Headings

  • Surgery
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Culture Test, Mixed
  • Isoantibodies
  • Immunohistochemistry
  • Heart Transplantation
  • Graft Rejection
  • Flow Cytometry
  • Chronic Disease