Abstract
Introduction Acute rejection currently accounts for 11% of the deaths of allograft recipients within the first six months of transplantation. Though endomyocardial biopsy is the most common method of detecting rejection, the procedure is highly invasive and expensive. MicroRNAs are RNA sequences that regulate gene expression and immune function and can be detected through tests of sera in blood. Previous studies have identified a correlation between microRNAs and acute rejection. This study hopes to address the usage of certain microRNAs as possible non-invasive biomarkers of acute cardiac cellular rejection. Methods We measured the expression of six different microRNAs (miR-146a, miR-155, miR-21, miR-30b, miR-30c, and miR-9) in 4 patients with rejection and in 16 healthy individuals. Using a Student’s t -test, miR-21 demonstrated a statistically significant difference in expression and was selected to test for expression in 12 heart allograft patients who did and did not experience acute cellular rejection, as defined by an ISHLT endomyocardial biopsy grade of 2R/3A on the day of serum collection. Chi-square analysis was used to compare expression levels between the two groups of patients and determine the accuracy of miR-21 levels in distinguishing between rejection and quiescence. Results Analysis of microRNA-21 levels showed significant up-regulation in patients with acute cellular rejection compared to patients without rejection. Patients with a minimum of 40% up-regulation were considered to be predictive for rejection. Rejection was predicted with 80% sensitivity, 100% specificity, a positive predictive value of 100% and negative predictive value of 98%, demonstrating high accuracy in determining rejection (P = 0.0001). Conclusions The study has shown that differential expression of microRNA-21 occurs in heart allograft patients experiencing rejection. Although further research will be done to determine the exact mechanism through which miR-21 affects rejection, it shows great promise as a non-invasive biomarker of cardiac transplant rejection.
Published Version
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