Background. This study aimed to identify serum microRNAs (miRNA) as a predictive tool for operational tolerance in pediatric liver transplantation (LT). Methods. Pediatric LT recipients were included in an immunosuppressant (IS) minimization protocol in our institution. Blood samples were collected at 2 stages: pre-protocol and post-completion. Ninety miRNAs expression was analyzed from blood samples using the NextAmp Analysis System and mirSCAN PanelChip (Quark Biosciences, Inc.). Participants were categorized into 3 groups: IS-free (complete withdrawal), IS-high (serum tacrolimus level > 2 ng/mL), and IS-low (serum tacrolimus level ≤ 2 ng/mL). Results. Between 2011 and 2019, 37 patients were enrolled in the IS minimization protocol at Taipei Veterans General Hospital. Of these, 13 patients (35.1%) successfully achieved IS-free status, whereas 24 (64.8%) remained non-IS-free. Eighteen patients with blood samples at pre-protocol and post-completion stage were included in the analysis. A total of 27 miRNAs exhibited significant differences in expression between the IS-free and IS-high groups at the pre-protocol stage. Additionally, 13 miRNAs showed significant changes in expression between the pre-protocol and post-completion stages in the IS-free group. miRNAs associated with immune suppression were expressed at higher levels in the IS-high group and at lower levels in the IS-free group at the pre-protocol stage. Conclusions. In this study, we identified 6 miRNAs—hsa-miR-21-5p, hsa-miR-22-3p, hsa-miR-30c-5p, hsa-miR-181b-5p, hsa-miR-20a-5p, and hsa-miR-125b-5p—that predict operational tolerance in pediatric LT at both the pre-protocol stage and during the minimization period. Notably, hsa-miR-125b-5p demonstrated perfect discriminative performance at the pre-protocol stage (area under the curve 1.00; sensitivity 100%; and specificity 100%) and showed significant changes in ΔCq between the pre-protocol and post-completion stages in the IS-free group. To our knowledge, this is the first report of miRNA biomarkers exhibiting such high accuracy for identifying operational tolerance in pediatric LT.
Hu et al. (Mon,) studied this question.