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

Author

Listed:
  • Jun Zeng

    (Sichuan University
    Sichuan University)

  • Ming Ma

    (Sichuan University
    Sichuan University
    Sichuan University)

  • Xiaojuan Jiang

    (Sichuan University)

  • Zhengsheng Rao

    (The Second Affiliated Hospital of Chongqing Medical University)

  • Dan Huang

    (Sichuan University
    Sichuan University)

  • Hao Zhang

    (Sichuan University
    Sichuan University)

  • Saifu Yin

    (Sichuan University
    Sichuan University)

  • Rong Bao

    (Sichuan University
    Sichuan University)

  • Haohan Zhang

    (Sichuan University
    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
    Sichuan University)

  • Keqin Zhang

    (The Second Affiliated Hospital of Chongqing Medical University)

  • Turun Song

    (Sichuan University
    Sichuan University)

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.

Suggested Citation

  • 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 & Turun Song, 2025. "Enzymatic conversion of blood group B kidney prevents hyperacute antibody-mediated injuries in ABO-incompatible transplantation," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56563-w
    DOI: 10.1038/s41467-025-56563-w
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    References listed on IDEAS

    as
    1. Rafi Chapanian & David H. Kwan & Iren Constantinescu & Fathima A. Shaikh & Nicholas A..A. Rossi & Stephen G Withers & Jayachandran N Kizhakkedathu, 2014. "Enhancement of biological reactions on cell surfaces via macromolecular crowding," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    2. Serena MacMillan & Sarah A. Hosgood & Léonie Walker-Panse & Peter Rahfeld & Spence S. Macdonald & Jayachandran N. Kizhakkedathu & Stephen G. Withers & Michael L. Nicholson, 2024. "Enzymatic conversion of human blood group A kidneys to universal blood group O," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
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