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Serum microRNA-181a-5p expression pattern correlates with acute cellular rejection in heart transplantation

Session Poster Session 6

Speaker Maria Generosa Crespo-Leiro

Event : ESC Congress 2019

  • Topic : heart failure
  • Sub-topic : Heart Transplantation
  • Session type : Poster Session

Authors : I Constanso (A Coruna,ES), L Nunez (A Coruna,ES), M Hermida-Prieto (A Coruna,ES), GM Marron-Linares (A Coruna,ES), E Alvarez-Lopez (A Coruna,ES), E Barge-Caballero (A Coruna,ES), MJ Paniagua-Martin (A Coruna,ES), G Barge-Caballero (A Coruna,ES), D Couto-Mallon (A Coruna,ES), J Pombo-Otero (A Coruna,ES), Z Grille-Cancela (A Coruna,ES), P Blanco-Canosa (A Coruna,ES), N Suarez-Fuentetaja (A Coruna,ES), JM Vazquez-Rodriguez (A Coruna,ES), MG Crespo-Leiro (A Coruna,ES)

I. Constanso1 , L. Nunez1 , M. Hermida-Prieto1 , G.M. Marron-Linares1 , E. Alvarez-Lopez1 , E. Barge-Caballero2 , M.J. Paniagua-Martin2 , G. Barge-Caballero2 , D. Couto-Mallon2 , J. Pombo-Otero3 , Z. Grille-Cancela2 , P. Blanco-Canosa2 , N. Suarez-Fuentetaja1 , J.M. Vazquez-Rodriguez2 , M.G. Crespo-Leiro2 , 1Instituto de Investigacion Biomedica A Coruna (INIBIC) - CHUAC - UDC - A Coruna - Spain , 2Complexo Hospitalario Universitario A Coruna, Department of Cardiology - A Coruna - Spain , 3Complexo Hospitalario Universitario A Coruna, Department of Anatomic Pathology - A Coruna - Spain ,

European Heart Journal ( 2019 ) 40 ( Supplement ), 3339

Background: Acute Cellular Rejection (ACR) remains a major complication in heart transplantation (HT). Since 1970, endomyocardial biopsy (EMB) has been the gold standard for ACR early detection. However, this invasive procedure has several limitations such as risk of complications, interobserver variability, false negative results and high cost. Therefore, a new non-invasive ACR biomarker is needed. Potential candidates could be microRNAs (miRs), small regulatory RNAs whose serum expression profiling could be modified in ACR patients. The aim of this study is the identification of differentially serum miRs expression patterns in ACR after HT.

Methods: Among HT performed in our Hospital (2013–2018), we selected patients with following criteria: i) “0R → 2R → 0R” EMB pattern for ACR (0R=no ACR, 2R=moderate ACR); ii) no antibody mediated rejection; iii) serum collected the same day as the EMBs. The 3 serum samples per patient matched in time with EMB were called “0Rs1 → 2Rs2 → 0Rs3”. In each of these serum samples, 179 miRs expression profile according manufacturer's instructions were analysed. Global Mean (GM) method was used to normalize our results expressed as miRs relative expression [2(–ΔCq)]. Expression pattern was defined as a 2 steps process: a significative rise (0Rs1 → 2Rs2) followed by a significative fall (2Rs2 → 0Rs3), or vice versa, in miR expression. Analysis of differences between 3 groups were calculated using one-way ANOVA with matched data and post-hoc Tukey test. ROC curve was generated for selected miRNA. A two-sided p<0.05 was considered statistically significant.

Results: 21 patients and their serum “0Rs1 → 2Rs2 → 0Rs3” samples were included in the study. Among 179 miRs analysed, 5 miRs showed significative difference between 0Rs1 and 2Rs2, 3 miRs were over-expressed (miR-181a-5p, miR-339-3p, let-7f-5p) and 2 under-expressed (miR-505-3p, miR-2110). Only miR-181a-5p met significative difference between 2Rs2 and 0Rs3 showing a statistical significative rise/fall pattern. Serum miR-181a-5p ROC analysis demonstrated significant discrimination between biopsy proven ACR from no-ACR biopsy, AUC=0.692 (p=0.0335).

Conclusion: Our findings suggest miR-181a-5p as a novel serological biomarker for detecting ACR after HT. After this preliminary discovery phase, miR-181a-5p is currently in a new validation phase to demonstrate its diagnostic performance.

Differentially expressed miRs
Mean relative expression 2(–ΔCq) (95% CI)Adjusted p-value (ANOVA)AUC (95% CI)
0Rs12Rs20Rs30Rs1 vs 2Rs22Rs2 vs 0Rs30Rs1 vs 0Rs3
miR-181–5p0.80 (0.60–1.02)1.11 (0.90–1.31)0.86 (0.71–1.01)0.01940.0225NS0.692 (0.529–0,855)
Relative Expression 2(–ΔCq) and AUC expressed as mean (95% Confident Interval). NS: not significative.

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