Tissue Expression of Programmed Cell Death 1 Ligand1 (PD-L1) in Biopsies of Transplant Livers of Pediatric Patients as a Possible Marker of Acute Cellular Rejection

Abstract

Introduction: Preclinical models have demonstrated that PD-1 and its ligand programmed death ligand1 (PD-L1) play significant roles in both graft induction and the maintenance of immune tolerance. It has also been suggested that PD-L1 tissue expression may predict graft rejection; however, the available data are sparse and inconclusive. Some studies were conducted on patients with cancer; most of them do not concern the liver, especially within the context of the use of immunohistochemical tests. Therefore, the aim of our study was to assess the relationship between tissue expression of PD-L1 in a unique material, i.e., in the liver biopsies of pediatric patients after transplantation with the presence of acute cellular rejection (ACR). Material and Methods: This retrospective study enrolled 55 biopsies from 55 patients who underwent protocol liver biopsies. The control group consisted of 19 biopsies from 13 patients diagnosed with acute cellular rejection (rejection activity index/RAI/ from 2 to 8). An immunohistochemical (IHC) staining for PD-L1 was performed in all of the liver specimens; its expression was analyzed in different regions of liver tissue (in inflammatory infiltrates and within the endothelium and hepatocytes). The following changes were re-evaluated in each specimen: features of any kind of rejection (acute cellular, antibody-mediated, chronic); the presence and severity of fibrosis (Ishak scale); and the presence of cholestasis and steatosis. Clinical parameters were also evaluated, including tests of liver function (AST, ALT, GGT, bilirubin). Results: The age of patients in the study group ranged from 2.37 to 18.9 years (median 13.87 years), with the time after transplantation being 1–17 years (median 8.36 years). The age of patients in the control group ranged from 1.48 to 17.51 years (median 7.93 years), with their biopsies being taken 0.62–14.39 years (median 1.33 years) after transplantation. We found a statistically significant relationship between PD-L1 expression on inflammatory infiltrates and ACR; however, there was no statistically significant relationship between PD-L1 endothelial expression and ACR. PD-L1 was not positive in the hepatocytes regardless of if it was the study or control group that was under observation. Conclusion: PD-L1 appears to be a promising marker to predict graft rejection.

Keywords

• pediatric liver transplantation
• liver biopsy
• PD-L1
• ACR
• immune tolerance