OR51: ANTIBODIES AGAINST PROTEASE-ACTIVATED RECEPTORS (PAR) AFTER IMMUNOSUPPRESSION WITHDRAWAL IN PEDIATRIC LIVING-DONOR LIVER TRANSPLANT

Abstract

Aim While the importance of non-HLA antibodies’ (Abs) pathological role has been emerging in kidney transplantation, the involvement of non-HLA Abs after liver transplantation remains poorly understood. Our study explored the effect of Abs against PAR in pediatric living-donor liver transplant (LDLT) patients after immunosuppression withdrawal (ISW). PAR are G protein-coupled receptors (GPCR) activated by proteolysis; their involvement in inflammatory pathologies has been indicated. Methods The study enrolled 69 pediatric LDLT patients; 16 achieved operational tolerance, 53 experienced rejection and/or fibrosis (intolerance) after ISW. Post-ISW sera (10.7 ± 4 years post) were screened for antibodies against two different PAR isoforms (PAR1 and PAR2) and against other GPCR using ELISA (CellTrend, Germany). Results Levels of Abs against PAR2 – but not PAR1 or other GPCR – were significantly higher in the intolerance group than in those tolerating ISW (P = 0.04). Further classification of the intolerance group showed that those who had rejection after ISW (median 2.2 years) had significantly higher levels of anti-PAR2 than those who developed fibrosis alone (median post-ISW 10.7 years) (P = 0.03). Comparison of anti-GPCR and liver function test results showed that, in the whole population, only anti-PAR2 had significant correlation with aspartate aminotransferase (R = 0.43, P Conclusions This is the first report to show that the Abs against PAR2 were detectable distinctively in patients who had rejection after ISW. The significant correlation of clinical parameters with higher levels of anti-PAR2 (but not the other anti-GPCR) may indicate a pathological role of anti-PAR2 in liver damage. Thus, the current findings may suggest a new aspect of non-HLA Abs against GPCR in liver transplantation. This hypothesis awaits the next step of studying how and when anti-PAR2 are developed after ISW. K. Schulze-Forster: Other (Identify); Company/Organization; CellTrend GmbH (owner). H. Heidecke: Other (Identify); Company/Organization; CellTrend GmbH (owner).