Sensing Acute Cellular Rejection in Liver Transplant Patients Using Liver-Derived Extracellular Particles: A...

Area of Science:

• Transplantation immunology
• Biomarker discovery
• Extracellular vesicle research

Background:

• Acute cellular rejection (ACR) following liver transplantation (LT) necessitates invasive liver biopsies for diagnosis.
• Current diagnostic methods for ACR are invasive, costly, time-consuming, and require specialized expertise.
• There is a critical need for non-invasive biomarkers to monitor ACR post-LT.

Purpose of the Study:

• To investigate the potential of peripheral liver-derived extracellular particles (EP) as a non-invasive biomarker for diagnosing ACR after LT.
• To identify specific EP subpopulations in blood plasma that correlate with ACR.
• To evaluate the diagnostic accuracy of these EP subpopulations for ACR detection.

Main Methods:

• In vitro studies using primary human hepatocytes under immunological stress to assess EP release.
• Analysis of EP concentrations in plasma from LT patients (n=11) before and during ACR.
• A diagnostic accuracy study (n=69) employing viSNE and FlowSOM algorithms to identify and characterize EP subpopulations.
• Quantification of a specific EP subpopulation (ASGR1+CD130+Annexin V+) for ACR prediction.

Main Results:

• In vitro experiments demonstrated organ-specific EP release from hepatocytes under stress.
• Elevated EP concentrations were observed in LT patients days preceding ACR.
• A specific EP subpopulation, ASGR1+CD130+Annexin V+, showed high diagnostic accuracy for ACR.
• This subpopulation achieved an area under the curve of 0.80, with 100% sensitivity and 68.5% specificity for predicting ACR.

Conclusions:

• Liver-derived extracellular particles (EP) in blood plasma represent a viable non-invasive biomarker for ACR diagnosis post-LT.
• The identified ASGR1+CD130+Annexin V+ EP subpopulation demonstrates significant potential for accurate ACR detection.
• This finding offers a promising alternative to invasive liver biopsies, potentially improving patient management and outcomes after liver transplantation.