Identification of Heart Transplant Rejection Subtypes With Circulating MicroRNAs

Area of Science:

• Transplantation immunology
• Biomarker discovery
• Molecular diagnostics

Background:

• Circulating microRNAs are potential biomarkers for acute cellular rejection (ACR) and antibody-mediated rejection (AMR) after heart transplantation.
• Assessing microRNA characteristics and diagnostic performance alongside clinical rejection scores (CRS) using blood samples at endomyocardial biopsy (EMB) is crucial.

Purpose of the Study:

• To evaluate the diagnostic accuracy of microRNAs and CRS for detecting ACR and AMR.
• To determine the predictive value of microRNA-based CRS for long-term transplant outcomes.

Main Methods:

• Prospective longitudinal cohort study (GRAfT) involving microRNA sequencing on blood samples from heart transplant recipients.
• Logistic regression modeling to develop ACR and AMR CRS based on previously identified microRNAs.
• Receiver-operating characteristic (ROC) curve analysis for diagnostic performance and Cox proportional hazard models for outcome prediction.

Main Results:

• High diagnostic performance for CRS: AUC 0.93 for ACR and 0.92 for AMR.
• Elevated CRS (threshold 65) demonstrated high sensitivity and specificity for both ACR and AMR.
• A 10-point increase in CRS was significantly associated with increased hazard for subsequent rejection, allograft dysfunction, or death.

Conclusions:

• Circulating microRNAs reliably identify ACR and AMR, correlating with EMB findings.
• MicroRNA-based CRS serves as a valuable noninvasive tool for screening and diagnosing rejection.
• Further validation could establish microRNA CRS as a substitute for EMB in managing heart transplant recipients.