miR-142-5p over-expression in blood and kidney graft from patients exhibiting chronic antibody mediated rejection

Richard Danger^1,2, Amélie Lavault², Magali Giral^2,3, Jean-Paul Duong Van Huyen⁴, Yohann Foucher¹, Annaick Pallier², Nicolas Degauque², Jean-Paul Soulillou^1,2,3, Sophie Brouard².

¹Université de Nantes, Faculté de Médecine, Nantes; ²Institut National de la Santé Et de la Recherche Médicale INSERM U643, and Institut de Transplantation Et de Recherche en Transplantation I.T.E.R.T., Nantes; ³Centre Hospitalier Universitaire Hôtel-Dieu, Nantes; ⁴Hôpital Européen Georges Pompidou, Paris; France.

Chronic antibody mediated rejection (CAMR) is characterized by specific histopathological lesions described by the BANFF classification and progressive but irreversible degradation of the kidney function despite immunosuppressive regimens. Gene expression modifications have been reported in organ biopsies as well as peripheral blood from transplanted recipients with CAMR which implicate de facto mechanisms of gene expression regulation during this process. Among gene expression regulating molecules, microRNA (miRNA), small non-coding RNA, have been clearly shown to be involved in various biological mechanisms and diseases. We performed miRNA expression profiling of 381 miRNA using Taqman low density arrays in total RNA from peripheral blood mononuclear cells from 9 patients with CAMR and 10 recipients with stable graft function (STA). Among the 231 miRNA expressed in at least half of samples for each groups, we highlighted on the differential expression of several miRNA involved in immune response including miR-142-5p, with a Mann-Whitney test corrected with a multitesting procedure. miR-142-5p over-expression was confirmed with individual qPCR assays on same PBMC samples (9 CAMR and 10 STA) and furthermore validated with 20 independent PBMC samples (10 CAMR or suspicious CAMR and 10 STA). We could not demonstrate a difference of miR-142-5p expression in PBMC from non-transplanted patients with terminal renal failure suggesting that the modulation of miR-142-5p in patients with CAMR is not due to renal dysfunction but rather related to immunological mechanisms. Moreover, miR-142-5p was also increased in biopsies from 5 CAMR patients compared to biopsies from 8 STA patients with normal histology. Altogether, these data suggest that miR-142-5p could be a biomarker of CAMR and may improve our understanding of chronic rejection mechanisms after transplantation.