Role of miR-29 as marker of risk of acute rejection after heart transplant

Background: Circulating miRNAs are potential biomarkers of the pathogenesis of certain diseases and in monitoring therapeutic responses. We hypothesized that serum miR-29 can determine risk of acute cardiac allograft rejection. Methods: Peripheral vein blood was collected from 50 healthy volunteers and 506 patients during post-transplant surveillance. Serum cardiac troponin I (cTnI) and miR-29 was detected by ELISA and qRT-PCR assay respectively. Rejection risk was defined as International Society of Heart and Lung Transplant score from leukocyte infiltration of an endomyocardial biopsy. No evidence of rejection was defined as grade R0, mild as R1, moderate as 2R and severe as 3R. Specificity and sensitivity of miR-29 to discriminate rejection was determined by the area under the curve (AUC) of receiver operating characteristic curve analysis. Correlations between miR29 and rejection grade were compared. Results: Serum miR-29 was 100.842.4 copies/mu l in R0 groups (P = 0.164 versus controls), 537.5 +/- 84.3 copies/mu l in R1 groups (P = 0.024) and 1478.4 +/- 198.7 copies/mu l in the joint R2/R3 groups (P = 0.001). MiR-29 was 1963.5 +/- 214.7 six months after transplantation, 1242.5 +/- 103.8 after a year, 825.6 +/- 58.2 after 2 years, 413.8 +/- 61.9 after 3 years and 270.6 +/- 34.6 ng/mL after 4 years (P < 0.001). The level of miR-29 correlated positively with cTnI, NT-proBNP, white blood cell counts, and negatively with lymphocyte counts (all P < 0.001). The AUC values (95% CI) for discriminating R0 and R1 was 0.81 (0.75-0.89), and was 0.79 (0.72-0.86) for R0 and R2/R3 (both P < 0.01). Conclusion: miR-29 is a promising predictor of the risk of heart transplant rejection.