December 18, 2014
Researchers identified four microRNAs with differential expression that can allow discrimination between normal and rejecting heart allografts.
Jean-Paul Duong Van Huyen, MD, PhD, and colleagues studied 113 recipients of heart transplants from four institutions; this included 60 patients in a test cohort and 53 in a validation cohort.
In the test cohort, the researchers compared patients with acute allograft rejection as verified by biopsy (n=30) vs. matched controls without rejection (n=30) by assessing microRNA expression in heart allograft tissue and concomitant serum. They further analyzed 14 microRNAs selected because of implication in allograft rejection, endothelial activation, and inflammation and tissue specificity.
The researchers identified seven microRNAs 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<.0001 for all comparisons).
Four microRNAs — miR-10a, miR-31, miR-92a and miR-155 — also showed differential serological expression that strongly correlated with tissue expression, according to the researchers. All four strongly discriminated patients with rejection from patients without rejection (miR-10a, area under the curve=0.975; miR-31, area under the curve=0.932; miR-92a, area under the curve 0.989; miR-155, area under the curve=0.998; P<.0001 for all comparisons).
In the validation cohort (31 with rejection, 22 without), all four microRNAs highly discriminated patients with rejection from patients without (P<.0001 for all comparisons), and the discrimination remained significant after adjustment for rejection diagnosis and time post-transplant.
“Taken together, our results suggest that these [microRNAs] are of potential clinical interest as noninvasive biomarkers of heart transplant rejection,” wrote Duong Van Huyen, from Paris Translational Research Center for Organ Transplantation, PARCC Cardiovascular Research Institute. “In heart transplantation, defining noninvasive and relevant biomarkers for allograft rejection is an unmet need.”
In a related editorial, Sandor Batkai, MD, PhD, and Thomas Thum, MD, PhD, both from Hannover Medical School, Germany, noted that acute rejection occurs in approximately 30% of heart transplant patients in the first year and in 1% to 7% of patients each year thereafter, but current diagnostic tools cannot reliably predict clinical outcomes, so biomarkers with better predictive potential are needed.
“These markers need to identify subgroups that can benefit from specific treatment options and that are at higher risk of toxicity or adverse effects, in order to improve organ–recipient matching and to improve outcomes,” they wrote. “[This] study … is a major step in the right direction.”
For more information:
Batkai S. Eur Heart J. 2014;35:3152-3154.
Duong Van Huyen JP. Eur Heart J. 2014;35:3194-3202.
Disclosure: The study was funded by Novartis Pharma France and Astellas France. The researchers, Batkai and Thum report no relevant financial disclosures.