Validation of the clinical utility of microRNA as noninvasive biomarkers of cardiac allograft rejection: A prospective longitudinal multicenter study

Guillaume Coutance; Maud Racapé; Guillaume Baudry; Lucien Lécuyer; François Roubille; Katrien Blanchart; Eric Epailly; Emmanuelle Vermes; Sabine Pattier; Aude Boignard; Arnaud Gay; Patrick Bruneval; Xavier Jouven; Jean-Paul Duong Van Huyen; Alexandre Loupy

doi:10.1016/j.healun.2023.07.010

Validation of the clinical utility of microRNA as noninvasive biomarkers of cardiac allograft rejection: A prospective longitudinal multicenter study

J Heart Lung Transplant. 2023 Nov;42(11):1505-1509. doi: 10.1016/j.healun.2023.07.010. Epub 2023 Jul 23.

Authors

Affiliations

¹ University of Paris, INSERM UMR 970, Paris Translational Research Centre for Organ Transplantation, Paris, France; Department of Cardiac and Thoracic Surgery, Cardiology Institute, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne University Medical School, Paris, France. Electronic address: [email protected].
² University of Paris, INSERM UMR 970, Paris Translational Research Centre for Organ Transplantation, Paris, France.
³ Department of Cardiac Surgery, University Hospital Bichat, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Cité, Paris, France.
⁴ Cardiology and Heart Transplant Department, Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ PhyMedExp, Cardiology Department, University of Montpellier, INSERM U1046, CNRS UMR, 9214; INI-CRT, Montpellier, France.
⁶ Cardiology Department, Caen University Hospital, Côte de Nacre, 14000 Caen, France.
⁷ Department of Cardiology and Cardiovascular Surgery, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
⁸ Department of Cardiology and Heart Transplantation Unit, CHRU Tours, France.
⁹ Department of Thoracic and Cardiovascular Surgery, Institut du Thorax, University Hospital, Nantes, France.
¹⁰ Department of Cardiology and Cardiovascular Surgery Department, Grenoble Alpes University Hospital, Grenoble, France.
¹¹ Thoracic and Cardiovascular Surgery Department, Rouen University Hospital, Rouen, France.
¹² University of Paris, INSERM UMR 970, Paris Translational Research Centre for Organ Transplantation, Paris, France; Cardiology and Heart Transplant Department, Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
¹³ University of Paris, INSERM UMR 970, Paris Translational Research Centre for Organ Transplantation, Paris, France; Pathology Department, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France.
¹⁴ University of Paris, INSERM UMR 970, Paris Translational Research Centre for Organ Transplantation, Paris, France; Kidney Transplant Department, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

PMID: 37487804
DOI: 10.1016/j.healun.2023.07.010

Abstract

While studies have shown an association between microRNAs and cardiac rejection, the clinical relevance of a preidentified miRNA signature as a noninvasive biomarker has never been assessed in prospective multicentric unselected cohorts. To address this unmet need, we designed a prospective study (NCT02672683) including recipients from 11 centers between August 2016 to March 2018. The objective was to validate the association between 3 previously identified circulating microRNA (10a, 92a, 155) and the histopathological diagnosis of rejection. Both relative and absolute (sensitivity analysis) quantifications of microRNAs were performed. Overall, 461 patients were included (831 biopsies, 79 rejections). A per-protocol interim analysis (258 biopsies, 49 rejections) did not find any association between microRNA and rejection (microRNA 10a: odds ratio (OR) = 1.05, 95% confidence intervals (CI) = 0.87-1.27, p = 0.61; 92a: OR = 0.98, 95%CI = 0.87-1.10, p = 0.68; 155: OR = 0.91, 95%CI = 0.76-1.10, p = 0.33). These results were confirmed in the sensitivity analysis. The analysis of the remaining sera was stopped for futility. This study shows no clinical utility of circulating microRNAs 10a, 92a, and 155 monitoring in heart allograft recipients.

Keywords: allograft rejection; endomyocardial biopsy; heart transplantation; noninvasive biomarker.