Enzymatic conversion of blood group B kidney prevents hyperacute antibody-mediated injuries in ABO-incompatible transplantation

Jun Zeng, Ming Ma, Xiaojuan Jiang, Zhengsheng Rao, Dan Huang, Hao Zhang, Saifu Yin, Rong Bao, Haohan Zhang, Zhiling Wang, Hongwei Gao, Feng Gong, Tao Lin (), Keqin Zhang () and Turun Song ()
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Jun Zeng: Sichuan University
Ming Ma: Sichuan University
Xiaojuan Jiang: Sichuan University
Zhengsheng Rao: The Second Affiliated Hospital of Chongqing Medical University
Dan Huang: Sichuan University
Hao Zhang: Sichuan University
Saifu Yin: Sichuan University
Rong Bao: Sichuan University
Haohan Zhang: Sichuan University
Zhiling Wang: The Second Affiliated Hospital of Chongqing Medical University
Hongwei Gao: Beijing Institute of Transfusion Medicine
Feng Gong: Beijing Institute of Transfusion Medicine
Tao Lin: Sichuan University
Keqin Zhang: The Second Affiliated Hospital of Chongqing Medical University
Turun Song: Sichuan University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Matching ABO blood group antigens between donors and recipients is critical to prevent hyperacute rejection in kidney transplantation. Enzymatic conversion of blood group antigens to the universal O type presents a promising strategy to overcome barriers in ABO-incompatible kidney transplantation. In this study, we employ α-galactosidase from Bacteroides fragilis to convert type B kidneys to type O during hypothermic machine perfusion. After 3 hours of perfusion with enzyme, more than 95% of blood group B antigens in the kidney endothelium are effectively removed. Subsequently, enzyme-treated kidneys are protected from antibody-mediated injuries in an ex vivo simulation of ABO-incompatible kidney transplantation. Encouraged by these results, a discarded type B kidney, following enzymatic conversion, is transplanted into a type O brain-dead recipient with high titer of anti-B antibody. The allograft survives for 63 hours without hyperacute rejection. Blood group B antigens re-express within 48 hours, with histopathological analyses indicating no evidence of antibody-mediated rejection. This enzymatic conversion approach holds the potential to broaden the practice of ABO-incompatible kidney transplantation, decrease waiting times and facilitate equitable organ allocation.

Date: 2025
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DOI: 10.1038/s41467-025-56563-w

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