Expression of miR-142-5p in peripheral blood mononuclear cells from renal transplant patients with chronic antibody-mediated rejection

• Published in: PloS one Vol. 8; no. 4; p. e60702
• Main Authors: Danger, Richard, Paul, Chloé, Giral, Magali, Lavault, Amélie, Foucher, Yohann, Degauque, Nicolas, Pallier, Annaïck, Durand, Maxim, Castagnet, Stéphanie, Duong Van Huyen, Jean-Paul, Delahousse, Michel, Renaudin, Karine, Soulillou, Jean-Paul, Brouard, Sophie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.04.2013; Public Library of Science (PLoS)
• Subjects: Analysis; Antibodies; Antibodies - immunology; Biology; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Biopsy; Blood; Blood cells; Cancer; Cell activation; Diagnosis; Gene expression; Gene Expression Regulation; Genes; Graft rejection; Graft Rejection - blood; Graft Rejection - genetics; Graft Rejection - immunology; Graft Rejection - pathology; Histology; Human health and pathology; Humans; Identification; Immunology; Kidney transplantation; Kidney Transplantation - adverse effects; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Life Sciences; Lymphocytes T; Medicine; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; miRNA; Modulation; Organ transplant recipients; Overexpression; Patients; Peripheral blood mononuclear cells; Rejection; Renal failure; Renal function; Ribonucleic acid; RNA; T cells; Time Factors; Transplantation; Transplants & implants; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060702

In renal transplantation, the unresponsiveness of patients undergoing chronic antibody mediated rejection (CAMR) to classical treatment stress on the need for accurate biomarkers to improve its diagnosis. We aim to determine whether microRNA expression patterns may be associated with a diagnosis of CAMR. We performed expression profiling of miRNAs in peripheral blood mononuclear cells (PBMC) of kidney transplant recipients with CAMR or stable graft function. Among 257 expressed miRNAs, 10 miRNAs associated with CAMR were selected. Among them, miR-142-5p was increased in PBMC and biopsies of patients with CAMR as well as in a rodent model of CAMR. The lack of modulation of miR-142-5p in PBMC of patients with renal failure, suggests that its over-expression in CAMR was associated with immunological disorders rather than renal dysfunction. A ROC curve analysis performed on independent samples showed that miR-142-5p is a potential biomarker of CAMR allowing a very good discrimination of the patients with CAMR (AUC = 0.74; p = 0.0056). Moreover, its expression was decreased in PHA-activated blood cells and was not modulated in PBMC from patients with acute rejection, excluding a non-specific T cell activation expression. The absence of modulation of this miRNA in immunosuppressed patients suggests that its expression was not influenced by treatment. Finally, the analysis of miR-142-5p predicted targets under-expressed in CAMR PBMC in a published microarray dataset revealed an enrichment of immune-related genes. Altogether, these data suggest that miR-142-5p could be used as a biomarker in CAMR and these finding may improve our understanding of chronic rejection mechanisms.