Article Dans Une Revue Kidney International Année : 2024

Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN)

1 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
2 Hôpital Necker - Enfants Malades [AP-HP]
3 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
4 Team 4 - U1064 Inserm - CR2TI - Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
5 ITERT - Institut de Transplantation et de Recherche en Transplantation [CHU Nantes]
6 BIH - Berlin Institute of Health
7 Charité - UniversitätsMedizin = Berlin University Medicine
8 LUBEM - Laboratoire Universitaire de Biodiversité et Ecologie Microbienne
9 AP-HP - Hopital Saint-Louis [AP-HP]
10 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
11 LVA - Laboratoire Vibrations Acoustique
12 CeLyA - centre Lyonnais d'Acoustique
13 Hôpital Lariboisière-Fernand-Widal [APHP]
14 UPCité - Université Paris Cité
15 Service d'Immunologie et d'Histocompatibilité
16 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
17 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
18 Vall d'Hebron University Hospital [Barcelona]
19 HUG - Hôpitaux universitaires de Genève = University Hospitals of Geneva
20 Service de néphrologie adultes [CHU Necker]
21 HU Berlin - Humboldt-Universität zu Berlin = Humboldt University of Berlin = Université Humboldt de Berlin
22 Hammersmith Hospital NHS Imperial College Healthcare
23 AOUB - IRCCS Azienda Ospedaliero-Universitaria di Bologna
24 Team 3 - U1064 Inserm - CR2TI - Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury
25 VHIR - Vall d’Hebron Research Institute
Sarhan Yaiche
  • Fonction : Auteur
Jacques Demotes
  • Fonction : Auteur
Harald Heidecke
  • Fonction : Auteur

Résumé

Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020. We prospectively assessed gene expression levels of 19 blood messenger RNAs, four antibodies targeting non-human leukocyte antigen (HLA) endothelial antigens, together with circulating anti-HLA donor-specific antibodies (DSA). The primary outcome was allograft rejection (antibody-mediated, T cell-mediated, or mixed) in the first year post-transplantation. Overall, 412 patients were included, with 812 biopsies paired with a blood sample. CD4 gene expression was significantly associated with rejection, while circulating anti-HLA DSA had a significant association with allograft rejection and a strong association with antibody-mediated rejection. All other tested biomarkers, including AKR1C3, CD3E, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1, as well as antibodies against angiotensin II type 1 receptor, endothelin 1 type A receptor, C3a and C5a receptors, did not show significant associations with allograft rejection. The blood messenger RNAs and non-HLA antibodies did not show an additional value beyond standard of care monitoring parameters and circulating anti-HLA DSA to predict allograft rejection in the first year post-transplantation. Thus, our results open avenues for specifically designed studies to demonstrate the clinical relevance and implementation of other candidate non-invasive biomarkers in kidney transplantation practice.
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inserm-04712412 , version 1 (27-09-2024)

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Valentin Goutaudier, Richard Danger, Rusan Ali Catar, Maud Racapé, Aurélie Philippe, et al.. Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN). Kidney International, 2024, S0085-2538 (24), pp.00565-00569. ⟨10.1016/j.kint.2024.07.027⟩. ⟨inserm-04712412⟩
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