Expression of miR-142-5p in Peripheral Blood Mononuclear Cells from Renal Transplant Patients with Chronic Antibody-Mediated Rejection

Abstract

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.

MiR-142-5p and miR-486-5p as biomarkers for early detection of chronic antibody-mediated rejection in kidney transplantation

“…However Mann Whitney U-test (supplemental figure 2A) It was reported that miR-142-5p expression increased in PBMCs from renal transplant patients with CAMR (Danger, Paul et al, 2013). We also observed that trend in clinical CAMR kidney transplant patient PBMCs, but not significantly different ( Figure 5).…”

Differential expression of microRNAs in renal transplant patients with acute T-cell mediated rejection

“…Furthermore, some studies showed that miR-142, miR-155, miR-223, miR-150 and miR-144 are highly specific for hematopoietic cell lineage [21]. A differential expression of miRNAs has been shown in patients with acute rejection [23,25,29,30], interstitial fibrosis [31,32], operationally tolerant patients [33], and chronic antibody mediated rejection [24]. To our knowledge, until now miR-142-3p and miR-155 expression analysis in the blood of patients with acute T-cell mediated rejection has not been performed yet.…”

“…In this study, we focused on miR-142-5p, miR-142-3p, miR-155 and miR-223 because of their specificity to hematopoietic lineage [23,24]; meanwhile there are some evidences on over-expression of these miRNAs in biopsy/PBMC samples of AR patients [24,25]. To our knowledge, the expression analysis of miR-142-3p and miR-155 in PBMC samples of ATCMR recipients and NA has not been performed yet.…”

Mesenchymal Stem Cells Alleviate LPS-Induced Acute Lung Injury in Mice by MiR-142a-5p-Controlled Pulmonary Endothelial Cell Autophagy

“…MiRNAs play a critical role in various physiological and pathological events. Among all miRNAs, miR-142a-5p is a newly recognized one and has just been associated with peripheral blood mononuclear cells that affect from chronic antibody-mediated rejection in renal transplant patients [22]. Its role in MSCs/ALI, however, has not been acknowledged.…”