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<p>ABO-incompatible kidney transplantation is widely used to meet the escalating need for organs. Current recipient-centric desensitization protocols involving antibody depletion through plasmapheresis increase the risk of infections, perioperative bleeding events and costs. Here we present a donor-centric desensitization protocol, converting type-A kidneys into enzyme-converted O kidneys during hypothermic perfusion to remove the A antigen from the kidneys. An ex vivo model resulted in no antibody-mediated injury. Encouraged by this, an enzyme-converted O kidney was transplanted into a type-O brain-dead recipient with a high titre of anti-A antibody, and no hyperacute rejection was observed. The graft was well tolerated with no evidence of antibody-mediated rejection for 2 days. Antibody-mediated lesions and complement deposition were found starting 3 days post-transplant, coinciding with A-antigen regeneration, and later higher Banff scores, suggesting an immune-mediated response. Single-cell sequencing confirms the elevated expression of accommodation-related genes, suggesting the potential for longer-term tolerance. This study provides a donor-centric organ engineering strategy and has the potential to broaden the reach of ABO-incompatible kidney transplantation, improving the fairness of and access to organ allocation.</p>

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Enzyme-converted O kidneys allow ABO-incompatible transplantation without hyperacute rejection in a human decedent model

  • 期刊论文

  • 发表日期：

    2025年10月3日

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  • Jun Zeng,
  • Ming Ma,
  • Ze Tao,
  • Zhengsheng Rao,
  • Chaomeng Wu,
  • Saifu Yin,
  • Xiaojuan Jiang,
  • Guo Chen,
  • Zhiling Wang,
  • Dan Huang,
  • Mengli Zhu,
  • Ling Liu,
  • Wenqian Huo,
  • Hao Yang,
  • Hui Guo,
  • Gang Chen,
  • Feng Li,
  • Chengyu Zheng,
  • Dajiu Huang,
  • Peter Rahfeld,
  • Jayachandran N. Kizhakkedathu,
  • Stephen G. Withers,
  • Xiaofeng Lu,
  • Keqin Zhang,
  • Tao Lin,
  • Turun Song

摘要

ABO-incompatible kidney transplantation is widely used to meet the escalating need for organs. Current recipient-centric desensitization protocols involving antibody depletion through plasmapheresis increase the risk of infections, perioperative bleeding events and costs. Here we present a donor-centric desensitization protocol, converting type-A kidneys into enzyme-converted O kidneys during hypothermic perfusion to remove the A antigen from the kidneys. An ex vivo model resulted in no antibody-mediated injury. Encouraged by this, an enzyme-converted O kidney was transplanted into a type-O brain-dead recipient with a high titre of anti-A antibody, and no hyperacute rejection was observed. The graft was well tolerated with no evidence of antibody-mediated rejection for 2 days. Antibody-mediated lesions and complement deposition were found starting 3 days post-transplant, coinciding with A-antigen regeneration, and later higher Banff scores, suggesting an immune-mediated response. Single-cell sequencing confirms the elevated expression of accommodation-related genes, suggesting the potential for longer-term tolerance. This study provides a donor-centric organ engineering strategy and has the potential to broaden the reach of ABO-incompatible kidney transplantation, improving the fairness of and access to organ allocation.