MicroRNAs as Non-invasive Biomarkers of Heart Transplant Rejection

Study Questions:

What is the efficacy of microRNA profiling as a noninvasive biomarker of cardiac allograft rejection?

Methods:

The investigators included 113 heart transplant recipients from four referral French institutions (test cohort, n = 60; validation cohort, n = 53). In the test cohort, they compared patients with acute biopsy-proven allograft rejection (n = 30) to matched control patients without rejection (n = 30), by assessing microRNA’s expression in the heart allograft tissue and patients’ concomitant serum using RNA extraction and qPCR analysis. Fourteen miRNAs were selected on the basis of their implication in allograft rejection, endothelial activation, and inflammation and tissue specificity.

Results:

The investigators identified seven miRNAs that were differentially expressed between normal and rejecting heart allografts: miR-10a, miR-21, miR-31, miR-92a, miR-142-3p, miR-155, and miR-451 (p < 0.0001 for all comparisons). Four out of seven miRNAs also showed differential serological expression (miR-10a, miR-31, miR-92a, and miR-155) with strong correlation with their tissular expression. The receiver-operating characteristic analysis showed that these four circulating miRNAs strongly discriminated patients with allograft rejection from patients without rejection: miR-10a (area under the curve [AUC] = 0.975), miR-31 (AUC = 0.932), miR-92a (AUC = 0.989), and miR-155 (AUC = 0.998, p < 0.0001 for all comparisons). They confirmed in the external validation set that these four miRNAs highly discriminated patients with rejection from those without. The discrimination capability of the four miRNAs remained significant when stratified by rejection diagnosis (T-cell-mediated rejection or antibody-mediated rejection) and time post-transplant.

Conclusions:

The authors concluded that a differential expression of miRNA occurs in rejecting allograft patients, not only at the tissue level but also in the serum, suggesting their potential relevance as noninvasive biomarkers in heart transplant rejection.

Perspective:

This study reports that four miRNAs showed differential tissue expression between rejecting and normal heart allografts. Furthermore, there were strong correlations between tissue and serological expression of these four miRNAs, and their assessment in patients’ sera permits discrimination with very high accuracy between patients with allograft rejection and those without. Taken together, these results suggest that these miRNAs are of potential clinical interest as noninvasive biomarkers of heart transplant rejection, and may help guide the clinical management of heart recipients in the future.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Heart Transplant

Keywords: Inflammation, Biological Markers, Graft Rejection, Gene Expression Profiling, Allografts, MicroRNAs, Transplantation, Homologous, Heart Transplantation, ESC Congress


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