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Foote JB, Jagdale A, Yamamoto T, et al. Histopathology of pig kidney grafts with/without expression of the carbohydrate Neu5Gc in immunosuppressed baboons. Xenotransplantation. 2021;doi: 10.1111/xen.12715.
Foote, J. B., Jagdale, A., Yamamoto, T., Hara, H., Bikhet, M. H., Schuurman, H. J., Nguyen, H. Q., Ezzelarab, M., Ayares, D., Anderson, D. J., Fatima, H., Eckhoff, D. E., Cooper, D. K. C., & Iwase, H. (2021). Histopathology of pig kidney grafts with/without expression of the carbohydrate Neu5Gc in immunosuppressed baboons. Xenotransplantation, . https://doi.org/10.1111/xen.12715
Foote, Jeremy B, et al. "Histopathology of pig kidney grafts with/without expression of the carbohydrate Neu5Gc in immunosuppressed baboons." Xenotransplantation vol. (2021). doi: https://doi.org/10.1111/xen.12715
Foote JB, Jagdale A, Yamamoto T, Hara H, Bikhet MH, Schuurman HJ, Nguyen HQ, Ezzelarab M, Ayares D, Anderson DJ, Fatima H, Eckhoff DE, Cooper DKC, Iwase H. Histopathology of pig kidney grafts with/without expression of the carbohydrate Neu5Gc in immunosuppressed baboons. Xenotransplantation. 2021 Oct 13; doi: 10.1111/xen.12715. Epub 2021 Oct 13. PMID: 34644438.
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Xenotransplantation. 2021 Oct 13; doi: 10.1111/xen.12715. Epub 2021 Oct 13.

Histopathology of pig kidney grafts with/without expression of the carbohydrate Neu5Gc in immunosuppressed baboons.

Xenotransplantation

Jeremy B Foote, Abhijit Jagdale, Takayuki Yamamoto, Hidetaka Hara, Mohamed H Bikhet, Henk-Jan Schuurman, Huy Q Nguyen, Mohamed Ezzelarab, David Ayares, Douglas J Anderson, Huma Fatima, Devin E Eckhoff, David K C Cooper, Hayato Iwase

Affiliations

  1. Department of Microbiology and Animal Resources Program, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  2. Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  3. Schubiomed Consultancy, Utrecht, The Netherlands.
  4. Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  5. Revivicor, Blacksburg, Virginia, USA.
  6. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  7. Department of Surgery, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA.

PMID: 34644438 DOI: 10.1111/xen.12715

Abstract

INTRODUCTION: Pigs deficient in three glycosyltransferase enzymes (triple-knockout [TKO] pigs, that is, not expressing the three known carbohydrate xenoantigens) and expressing 'protective' human transgenes are considered a likely source of organs for transplantation into human recipients. Some human sera have no or minimal natural antibody binding to red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) from TKO pigs. However, all Old World monkeys exhibit natural antibody binding to TKO pig cells. The xenoantigen targets of Old World monkey natural antibodies are postulated to be carbohydrate moieties exposed when the expression of the carbohydrate N-glycolylneuraminic acid (Neu5Gc) is deleted. The aim of this study was to compare the survival in baboons and histopathology of renal grafts from pigs that either (a) expressed Neu5Gc (GTKO pigs; Group 1) or (b) did not express Neu5Gc (GTKO/CMAHKO [DKO] or TKO pigs; Group 2).

METHODS: Life-supporting renal transplants were carried out using GTKO (n = 5) or DKO/TKO (n = 5) pig kidneys under an anti-CD40mAb-based immunosuppressive regimen.

RESULTS: Group 1 baboons survived longer than Group 2 baboons (median 237 vs. 35 days; mean 196 vs. 57 days; p < 0.07) and exhibited histopathological features of antibody-mediated rejection in only two kidneys. Group 2 exhibited histopathological features of antibody-mediated rejection in all five grafts, with IgM and IgG binding to renal interstitial arteries and peritubular capillaries. Rejection-free survival was significantly longer in Group 1 (p < 0.05).

CONCLUSIONS: The absence of expression of Neu5Gc on pig kidney grafts is associated with increased binding of baboon antibodies to pig endothelium and reduced graft survival.

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords: N-glycolylneuraminic acid; Neu5Gc; baboon; genetically-engineered; histopathology; kidney; pig; xenotransplantation

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