Abstract 14074: Unique Circulating microRNA Profile in Pediatric Heart Transplant Recipients

Abstract

Introduction: MicroRNAs (miRs) are small noncoding RNAs capable of modulating the expression of many genes. Hypothesis: Our hypothesis was that circulating miRs would be a biomarker of acute cellular rejection (ACR) in pediatric heart transplant recipients (PHTR). Methods: An array for 381 miRs was performed using serum from 52 PHTR and 21 healthy pediatric controls (HC). ACR was defined as ISHLT biopsy score ≥2R. Patients with antibody mediated rejection were excluded. RNA was extracted using the miRNeasy Mini Kit (Qiagen), and arrays were performed using the TaqMan Open Array miR panel (Thermo Fisher Scientific). Statistical analysis included Random Forest (RF) with area under the receiver operator curve (AUC) based on the top 3 differentiating miRs by RF, and Wilcoxon rank-sum t-test (significant q-value < 0.05). Results: Of the 52 PHTR, median age 8.5 years, 44% female, race/ethnicity white in 83%, 12% African American, 13% Asian/other, and 13% Hispanic; 22 PHTR had ACR at time of serum collection. There were 21 HC, median age 5.6 years, 38% female, race/ethnicity white in 76%, 24% Asian/other, and 19% Hispanic. There were 66 miRs significantly different between HC and all PHTR (AUC of 0.91). For HC vs PHTR without ACR there were 50 differential miRs (AUC of 0.94), and for HC vs PHTR with ACR there were 51 differential miRs (AUC 0.96). Table 1 demonstrates miRs that are differentially expressed compared to HC based on the presence or absence of ACR. Circulating miRs were not different between PHTR with (n=22) and without ACR (n=30). Conclusions: The circulating miR profile of PHTR is unique compared to HC, suggesting a strong influence of the transplant mileu on miR expression. There were 17 miRs with differential expression compared to HC based on the presence or absence of ACR. These results support future investigations in larger populations to determine if circulating miRs could serve as biomarkers of ACR in PHTR, and whether these miRs contribute to the pathophysiology of ACR.