| Autor: |
Xiang Fei Cheng, Christine McMahon, C. Avon, Agnes M. Azimzadeh, Tianshu Zhang, T. Stoddard, E. Welty, Richard N. Pierson, Mitch Higuchi, Shahrooz S. Kelishadi, Amal Laaris |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Journal of Clinical Investigation. 120:1275-1284 |
| ISSN: |
0021-9738 |
| DOI: |
10.1172/jci41861 |
| Popis: |
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 (alphaCD20) 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 alphaCD20 or CsA alone. In animals treated with both alphaCD20 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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