Impact of HLA evolutionary divergence and donor-recipient molecular mismatches on antibody-mediated rejection of kidney allografts

Zeynep Demir, Marc Raynaud, Gillian Divard, Kevin Louis, Agathe Truchot, Matthias Niemann, Renata Ponsirenas, Olivier Aubert, Arnaud Del Bello, Alexandre Hertig, Dany Anglicheau, Bethany Dale, Nassim Kamar, Massimo Mangiola, Adriana Zeevi, Carmen Lefaucheur and Alexandre Loupy ()
Additional contact information
Zeynep Demir: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration
Marc Raynaud: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration
Gillian Divard: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration
Kevin Louis: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration
Agathe Truchot: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration
Matthias Niemann: PIRCHE AG
Renata Ponsirenas: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration
Olivier Aubert: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration
Arnaud Del Bello: University Paul Sabatier
Alexandre Hertig: Foch Hospital
Dany Anglicheau: Assistance Publique—Hôpitaux de Paris
Bethany Dale: PIRCHE AG
Nassim Kamar: University Paul Sabatier
Massimo Mangiola: NYU Langone Health
Adriana Zeevi: University of Pittsburgh Medical Center
Carmen Lefaucheur: Assistance Publique—Hôpitaux de Paris
Alexandre Loupy: Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Several in-silico methods emerge to assess HLA immunogenicity and stratify immunological risk, including HLA molecular mismatches and HLA evolutionary divergence (HED). However, their added value in risk-stratifying antibody-mediated rejection (AMR) remains uncertain. We include 5159 kidney transplant recipients from four centers. Thirty-three clinical and immunological parameters are assessed, including HLA eplet mismatches, PIRCHE-II scores, and HED. Their associations with AMR are evaluated using Cox models. AMR occurrs in 1024 patients (19.9%). Immunological determinants of AMR include anti-HLA DSA (MFI:500-1400, HR:1.87; MFI > 1400, HR:3.84, p

Date: 2025
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DOI: 10.1038/s41467-025-60485-y

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