Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

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Abstract

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans.

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Figure 1: Elicited antibodies to non-Gal antigens lead to AHXR of GalT-KO kidney grafts.

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Acknowledgements

The authors thank Revivicor Inc. for providing GalT-KO pigs, Fujisawa Canada for the donation of tacrolimus, Sangstat for providing Thymoglobulin and Bayer Canada for providing IVIG. We appreciate editorial assistance from C. Abbott and secretarial support from S. Mutch and T. Mangan. This work was supported by the Ontario Research Development Challenge Fund; Multi-Organ Transplant Program, London Health Sciences Centre; Fujisawa Canada, US National Institutes of Health grant R01DK64207, AI38899 (to T.S.); and an unrestricted gift to the Thomas E. Starzl Transplantation Institute from the Eberly Family Fund for Transplant Innovation.

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Correspondence to Thomas Starzl or Robert Zhong.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Both endothelial cells (EC) and lymphocytes (LC) isolated from GalT-KO donor pigs had undetectable Gal expression. (PDF 45 kb)

Supplementary Fig. 2

Changes in lymphocyte counts, platelet counts and urine protein levels of each recipient after transplantation. (PDF 84 kb)

Supplementary Fig. 3

No significant changes were seen in the levels of both Gal-specific IgG and IgM after transplantation in a representative baboon. (PDF 76 kb)

Supplementary Methods (PDF 61 kb)

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Chen, G., Qian, H., Starzl, T. et al. Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys. Nat Med 11, 1295–1298 (2005) doi:10.1038/nm1330

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