COMPREHENSIVE IMMUNOPHENOTYPING OF TREGS AND SERUM CYTOKINES MAY HELP TO DISTINGUISH HCV HEPATITIS FROM REJECTION IN LIVER TRANSPLANT PATIENTS

Chronic HCV infection is one of the main indications for liver transplantation (LTx) in developed countries and the reinfection of the graft is almost universal. The differentiation between graft hepatitis due to HCV and rejection is a challenging problem demanding opposing therapeutic strategies. The aim of this study was to investigate if characteristics of regulatory T cells (Tregs) and plasma biomarkers differ in graft hepatitis C and rejection. Methods: 31 patients that underwent LTx were enrolled in a prospective observational study. All patients received protocol liver biopsies and PBMCs and plasma were collected at the same time points. Peripheral Tregs were analysed for frequency, phenotype and functional markers, using a multicolour approach with surface and intracellular markers (CD4, CD25, FoxP3, CD127, CCR7, CD45RA, CD39, CD 49d, ICOS and TGFβ) by flow cytometry (BD LSR-II). In addition 27 cytokines and chemokines were measured in plasma using the multiplex technology (Bio-Plex System). Results: Phenotypical and functional characteristics of Tregs showed a high inter-individual variability. HCV-infected liver transplant recipients showed a higher percentage of TGFβ+Tregs than HCV-negative transplanted patients. HCV-infected transplant patients with histological evidence of rejection displayed a lower number of TGFβ+Tregs than individuals with HCV-associated graft hepatitis. Furthermore, two of the analysed chemokines (CXCL10/IP–10 and CCL4/MIP1β) showed an AUC >0,8 and could predict a graft rejection with a sensitivity of 100% and a specificity of 87,5% and 75% respectively. Conclusions: The immunophenotypical characteristics of the Tregs together with a distinct plasma cytokine pattern could be useful in distinguishing HCV-hepatitis from rejection in liver transplant recipients. These, yet preliminary findings could prove to be useful in the management of liver transplanted patients and should be applied in larger patient cohorts.

HCV - Liver transplantation - Tregs - chemokines - cytokines