Xavier Verhelst1, Anja Geerts1, Ina Jochmans2, Dieter Vanderschaeghe3, Agnes Paradissis1, Aude Vanlander4, Frederik Berrevoet4, Géraldine Dahlqvist5, Frederik Nevens6, Jacques Pirenne2, Xavier Rogiers4, Nico Callewaert3, Roberto I Troisi4, Hans Van Vlierberghe7. 1. Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium; Laboratory of Hepatology Research, Ghent University, Ghent, Belgium. 2. Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium; Laboratory of Abdominal Transplantation, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. 3. VIB-Ugent Center for Medical Biotechnology and Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium. 4. Department of General, Hepatobiliary and Liver Transplantation Surgery, Ghent, Belgium; University Hospital Medical School, Ghent, Belgium. 5. Hepatology, UCL Saint-Luc, Brussels, Belgium. 6. Department of Hepatology, University Hospitals, Leuven, Belgium. 7. Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium; Laboratory of Hepatology Research, Ghent University, Ghent, Belgium. Electronic address: hans.vanvlierberghe@uzgent.be.
Abstract
BACKGROUND & AIMS: Primary nonfunction (PNF) is a rare complication after liver transplantation that requires urgent retransplantation. PNF is associated with livers from extended criteria donors. Clinical and biochemical factors have not been identified that reliably associate with graft function after liver transplantation. Serum patterns of N-glycans associate with changes in the liver. We analyzed perfusate from grafted liver to identify protein glycosylation patterns associated with PNF. METHODS: We performed a prospective study of consecutive patients who underwent liver transplantation (66 patients, from 1 center, in the derivation set, and 56 patients, from 2 centers, in the validation set) in Belgium, from October 1, 2011, through April 30, 2017. All donor grafts were transported using cold static storage, and perfusate samples were collected from the livers by flushing of hepatic veins before transplantation. Protein-linked N-glycans were isolated from perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer. We compared glycan patterns between patients with vs without PNF of transplanted livers. PNF was defined as the need for urgent retransplantation when a graft had no evidence of function, after exclusion of other causes, such as hepatic artery thrombosis or acute cellular rejection. RESULTS: The relative abundance of a single glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan (NGA2F) was significantly increased in perfusate of livers given to 4 patients who developed PNF after liver transplantation compared with livers given to patients who did not develop PNF. Level of NGA2F identified patients with PNF with 100% accuracy. This glycomarker was the only factor associated with PNF in multivariate analysis in the derivation and the validation sets (P < .0001). CONCLUSIONS: In an analysis of patients who underwent liver transplantation, we associated graft perfusate level of glycan NGA2F present on perfusate proteins with development of PNF with 100% accuracy, and validated this finding in a separate cohort of patients. This biomarker might be used to assess grafts before transplantation, especially when high-risk organs are under consideration.
BACKGROUND & AIMS: Primary nonfunction (PNF) is a rare complication after liver transplantation that requires urgent retransplantation. PNF is associated with livers from extended criteria donors. Clinical and biochemical factors have not been identified that reliably associate with graft function after liver transplantation. Serum patterns of N-glycans associate with changes in the liver. We analyzed perfusate from grafted liver to identify protein glycosylation patterns associated with PNF. METHODS: We performed a prospective study of consecutive patients who underwent liver transplantation (66 patients, from 1 center, in the derivation set, and 56 patients, from 2 centers, in the validation set) in Belgium, from October 1, 2011, through April 30, 2017. All donor grafts were transported using cold static storage, and perfusate samples were collected from the livers by flushing of hepatic veins before transplantation. Protein-linked N-glycans were isolated from perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer. We compared glycan patterns between patients with vs without PNF of transplanted livers. PNF was defined as the need for urgent retransplantation when a graft had no evidence of function, after exclusion of other causes, such as hepatic artery thrombosis or acute cellular rejection. RESULTS: The relative abundance of a single glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan (NGA2F) was significantly increased in perfusate of livers given to 4 patients who developed PNF after liver transplantation compared with livers given to patients who did not develop PNF. Level of NGA2F identified patients with PNF with 100% accuracy. This glycomarker was the only factor associated with PNF in multivariate analysis in the derivation and the validation sets (P < .0001). CONCLUSIONS: In an analysis of patients who underwent liver transplantation, we associated graft perfusate level of glycan NGA2F present on perfusate proteins with development of PNF with 100% accuracy, and validated this finding in a separate cohort of patients. This biomarker might be used to assess grafts before transplantation, especially when high-risk organs are under consideration.
Authors: Alexander McQuiston; Amir Emtiazjoo; Peggi Angel; Tiago Machuca; Jason Christie; Carl Atkinson Journal: Front Immunol Date: 2021-08-11 Impact factor: 7.561