MicroRNA Profiling as a Novel Predictive Tool for Operational Tolerance in Pediatric Liver Transplantation: A...

Area of Science:

• Transplantation immunology
• Molecular diagnostics
• Pediatric medicine

Background:

• Operational tolerance is crucial for long-term success in pediatric liver transplantation (LT).
• Minimizing immunosuppressant (IS) drugs is a key goal to reduce toxicity and improve patient outcomes.
• Identifying reliable biomarkers for operational tolerance is essential for guiding IS minimization protocols.

Purpose of the Study:

• To identify serum microRNAs (miRNAs) as predictive biomarkers for operational tolerance in pediatric liver transplant recipients.
• To evaluate the diagnostic accuracy of specific miRNAs in distinguishing between IS-free and IS-dependent states.
• To assess the utility of miRNAs in monitoring the success of immunosuppressant minimization protocols.

Main Methods:

• Serum samples were collected from pediatric LT recipients undergoing IS minimization at pre-protocol and post-completion stages.
• MicroRNA expression profiling was performed using the NextAmp Analysis System and mirSCAN PanelChip.
• Participants were classified into IS-free, IS-high (>2 ng/mL tacrolimus), and IS-low (≤2 ng/mL tacrolimus) groups.

Main Results:

• A total of 37 pediatric LT recipients were enrolled; 13 (35.1%) achieved IS-free status.
• Significant differences in miRNA expression were observed between IS-free and IS-high groups at the pre-protocol stage (27 miRNAs) and within the IS-free group during minimization (13 miRNAs).
• MiRNAs associated with immune suppression were differentially expressed, with higher levels in IS-high and lower levels in IS-free groups pre-protocol.

Conclusions:

• Six specific 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) were identified as predictors of operational tolerance in pediatric LT.
• hsa-miR-125b-5p demonstrated exceptional predictive performance (AUC 1.00, 100% sensitivity, 100% specificity) at the pre-protocol stage.
• These findings represent the first report of highly accurate miRNA biomarkers for predicting operational tolerance in pediatric liver transplantation, supporting safer IS minimization.