Bortezomib, C1-inhibitor and plasma exchange do not prolong the survival of multi-transgenic GalT-KO pig kidney xenografts in baboons

S. Le Bas-Bernardet, X. Tillou, J. Branchereau, N. Dilek, N. Poirier, M. Chatelais, B. Charreau, D. Minault, J. Hervouet, K. Renaudin, C. Crossan, L. Scobie, Y. Takeuchi, M. Diswall, M.E. Breimer, N. Klar, M.R. Daha, P. Simioni, S.C. Robson, M.B. NottleE.J. Salvaris, P.J. Cowan, A.J.F. d'Apice, D.H. Sachs, K. Yamada, I. Lagutina, R. Duchi, A. Perota, G. Lazzari, C. Galli, E. Cozzi, J.‐P. Soulillou, B. Vanhove, G. Blancho

Research output: Contribution to journalArticle

Abstract

Galactosyl-transferase KO (GalT-KO) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. We have performed life supporting kidney xenotransplantation into baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human C1 inhibitor combined with cyclophosphamide or bortezomib with or without 2–3 plasma exchanges. One baboon received a control GalT-KO xenograft with the latter immunosuppression. All immunosuppressed baboons rejected the xenografts between days 9 and 15 with signs of acute humoral rejection, in contrast to untreated controls (n¿=¿2) that lost their grafts on days 3 and 4. Immunofluorescence analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d staining, indicating classical complement pathway blockade but alternate pathway activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage infiltration with minimal lymphocyte representation.
Original languageEnglish
Pages (from-to)358–370
Number of pages13
JournalAmerican Journal of Transplantation
Volume15
Issue number2
Early online date22 Jan 2015
DOIs
Publication statusPublished - Feb 2015

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Keywords

  • xenotransplantation
  • immunosuppression
  • xenografts
  • genetics

Cite this

Le Bas-Bernardet, S., Tillou, X., Branchereau, J., Dilek, N., Poirier, N., Chatelais, M., Charreau, B., Minault, D., Hervouet, J., Renaudin, K., Crossan, C., Scobie, L., Takeuchi, Y., Diswall, M., Breimer, M. E., Klar, N., Daha, M. R., Simioni, P., Robson, S. C., ... Blancho, G. (2015). Bortezomib, C1-inhibitor and plasma exchange do not prolong the survival of multi-transgenic GalT-KO pig kidney xenografts in baboons. American Journal of Transplantation, 15(2), 358–370. https://doi.org/10.1111/ajt.12988