Coutance Guillaume, Racapé Maud, Baudry Guillaume, Lécuyer Lucien, Roubille François, Blanchart Katrien, Epailly Eric, Vermes Emmanuelle, Pattier Sabine, Boignard Aude, Gay Arnaud, Bruneval Patrick, Jouven Xavier, Duong Van Huyen Jean-Paul, Loupy Alexandre
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.
University of Paris, INSERM UMR 970, Paris Translational Research Centre for Organ Transplantation, Paris, France.
J Heart Lung Transplant. 2023 Nov;42(11):1505-1509. doi: 10.1016/j.healun.2023.07.010. Epub 2023 Jul 23.
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.
虽然研究已表明微小RNA与心脏排斥反应之间存在关联，但预先确定的微小RNA特征作为一种非侵入性生物标志物的临床相关性从未在前瞻性多中心未选择队列中进行评估。为满足这一未被满足的需求，我们设计了一项前瞻性研究（NCT02672683），纳入了2016年8月至2018年3月期间来自11个中心的接受者。目的是验证3种先前确定的循环微小RNA（10a、92a、155）与排斥反应的组织病理学诊断之间的关联。对微小RNA进行了相对和绝对（敏感性分析）定量。总体而言，纳入了461例患者（831次活检，79次排斥反应）。一项符合方案的中期分析（258次活检，49次排斥反应）未发现微小RNA与排斥反应之间存在任何关联（微小RNA 10a：比值比（OR）=1.05，95%置信区间（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）。这些结果在敏感性分析中得到了证实。对其余血清的分析因无效而停止。本研究表明，监测心脏移植受者循环微小RNA 10a、92a和155没有临床实用性。
