Enzymatic conversion of human blood group A kidneys to universal blood group O
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 30. März, Seite 2795 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
MacMillan, Serena [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 02.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-47131-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370449126 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Hosgood, Sarah A |e verfasserin |4 aut | |
| 700 | 1 | |a Walker-Panse, Léonie |e verfasserin |4 aut | |
| 700 | 1 | |a Rahfeld, Peter |e verfasserin |4 aut | |
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| 700 | 1 | |a Kizhakkedathu, Jayachandran N |e verfasserin |4 aut | |
| 700 | 1 | |a Withers, Stephen G |e verfasserin |4 aut | |
| 700 | 1 | |a Nicholson, Michael L |e verfasserin |4 aut | |
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