[Purpose] All donor specific antibodies (DSAs) cannot cause chronic antibody-mediated rejection (CAMR), as grafts of renal transplant recipients with DSAs have shown different outcomes. Although CAMR should be detected before renal dysfunction is observed, definitive diagnosis requires a graft biopsy. Non-invasive biomarkers are highly desirable. MicroRNA (miRNA) are non-cording small RNA that repressed protein translation through inhibition of protein synthesis or mRNA degradation. The main objective of the study is to analyze the predictive value of PBMCs miRNAs for development of CAMR.
[Method] (i) To assess the impact of risk factor on PBMCs miRNA levels, we conducted a global miRNA expression analysis using pooled RNA, isolated from PBMCs of patients with DSA + CAMR (CR, n=6), with DSA + stable graft function (Potential Risk: PR, n=11), and with no DSA + stable function (Stable: ST, n=11). Total 435 mature human miRNAs were profiled. (ii) Next, biopsy-proven CAMR (n=5) and non-CAMR (n=4) were analyzed in another subject of PR group.
[Result] (i) In the initial screen, the levels of 9 miRNAs differed more than 2-fold between CR/PR vs ST (candidates for DSA-producing biomarker), and 3 miRNAs differed more than 2-fold between CR vs PR/ST (candidates for CAMR biomarker). An independent set of 33 PBMC from 28 patients (6 CR 11 PR, and 11 ST) and 5 healthy volunteers was used to validate a subset of miRNAs. We identified miR-142-5p as a DSA producing (CR=PR<ST) and miR-182 as a CAMR biomarker (CR>PR=ST) miRNA. (ii) Among patients with DSA + stable function, miR-182 expression levels in PBMC from biopsy-proven 5 CR patients was higher than those from 4 non-rejected patients.
[Discussion] It was suggested that PBMCs miRNA profiles could distinguish kidney transplant patients according to DSA status (miR-142-5p) and development of subclinical CAMR (miR-182). Our observations support the hypothesis that miRNA expression patterns in PBMCs may serve as biomarkers of human kidney allograft status.
To cite this abstract in AMA style:Iwasaki K, Ping J, Yamamoto T, Miwa Y, Haneda M, Watarai Y, Katayama A, Uchida K, Kobayashi T. Analysis of miRNAs in Peripheral Blood Mononuclear Cells: Potential Value of miR-182 as a Biomarker of Chronic Antibody Mediated Rejection [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/analysis-of-mirnas-in-peripheral-blood-mononuclear-cells-potential-value-of-mir-182-as-a-biomarker-of-chronic-antibody-mediated-rejection/. Accessed December 1, 2020.
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