Enzymatic conversion of human blood group A kidneys to universal blood group O.

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

Nature communications 2024 Mar 30

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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. © 2024. The Author(s).

Citation

Serena MacMillan, Sarah A Hosgood, Léonie Walker-Panse, Peter Rahfeld, Spence S Macdonald, Jayachandran N Kizhakkedathu, Stephen G Withers, Michael L Nicholson. Enzymatic conversion of human blood group A kidneys to universal blood group O. Nature communications. 2024 Mar 30;15(1):2795