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MacMillan, Serena; Hosgood, Sarah A.; Walker-Panse, Léonie; Rahfeld, Peter; Macdonald, Spence S.; Kizhakkedathu, Jayachandran N.; Withers, Stephen G.; Nicholson, Michael L.

ABO blood group compatibility restrictions present the first barrier to donor-recipient matching in kidney transplantation. Here, we present the use of two enzymes, FpGalNAc deacetylase and FpGalactosaminidase, from the bacterium Flavonifractor plautii to enzymatically convert blood group A antigens from the renal vasculature of human kidneys to ‘universal’ O-type. Using normothermic machine perfusion (NMP) and hypothermic machine perfusion (HMP) strategies, we demonstrate blood group A antigen loss of approximately 80% in as little as 2 h NMP and HMP. Furthermore, we show that treated kidneys do not bind circulating anti-A antibodies in an ex vivo model of ABO-incompatible transplantation and do not activate the classical complement pathway. This strategy presents a solution to the donor organ shortage crisis with the potential for direct clinical translation to reduce waiting times for patients with end stage renal disease.

Text

2024-11-26

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89717

MacMillan, S., Hosgood, S.A., Walker-Panse, L. et al. Enzymatic conversion of human blood group A kidneys to universal blood group O. Nat Commun 15, 2795 (2024).

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http://creativecommons.org/licenses/by-nc-nd/4.0/