Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys

Shahrooz S. Kelishadi, Agnes M. Azimzadeh, Tianshu Zhang, Tiffany Stoddard, Emily Welty, Christopher Avon, Mitch Higuchi, Amal Laaris, Xiang Fei Cheng, Christine McMahon, Richard N. Pierson

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Chronic rejection currently limits the long-term efficacy of clinical transplantation. Although B cells have recently been shown to play a pivotal role in the induction of alloimmunity and are being targeted in other transplant contexts, the efficacy of preemptive B cell depletion to modulate alloimmunity or attenuate cardiac allograft vasculopathy (CAV) (classic chronic rejection lesions found in transplanted hearts) in a translational model has not previously been described. We report here that the CD20-specific antibody (αCD20) rituximab depleted CD20+ B cells in peripheral blood, secondary lymphoid organs, and the graft in cynomolgus monkey recipients of heterotopic cardiac allografts. Furthermore, CD20+ B cell depletion therapy combined with the calcineurin inhibitor cyclosporine A (CsA) prolonged median primary graft survival relative to treatment with αCD20 or CsA alone. In animals treated with both αCD20 and CsA that achieved efficient B cell depletion, alloantibody production was substantially inhibited and the CAV severity score was markedly reduced. We conclude therefore that efficient preemptive depletion of CD20+ B cells is effective in a preclinical model to modulate pathogenic alloimmunity and to attenuate chronic rejection when used in conjunction with a conventional clinical immunosuppressant. This study suggests that use of this treatment combination may improve the efficacy of transplantation in the clinic.

Original languageEnglish (US)
Pages (from-to)1275-1284
Number of pages10
JournalJournal of Clinical Investigation
Volume120
Issue number4
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Preemptive CD20<sup>+</sup> B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys'. Together they form a unique fingerprint.

  • Cite this

    Kelishadi, S. S., Azimzadeh, A. M., Zhang, T., Stoddard, T., Welty, E., Avon, C., Higuchi, M., Laaris, A., Cheng, X. F., McMahon, C., & Pierson, R. N. (2010). Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys. Journal of Clinical Investigation, 120(4), 1275-1284. https://doi.org/10.1172/JCI41861