title: Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.
abstract: Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.
authors.affiliation: Faculty of Life Sciences &Medicine, King's College London, London, United Kingdom.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Faculty of Life Sciences &Medicine, King's College London, London, United Kingdom.|Department of Analytical Chemistry, Nutrition and Food Science, University of Salamanca, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Casas-Ferreira
authors.affiliation: King's College Hospital, King's College London, London, United Kingdom.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Faculty of Life Sciences &Medicine, King's College London, London, United Kingdom.
authors.forename: Arundhuti
authors.initials: A
authors.lastname: Sen
authors.affiliation: Faculty of Life Sciences &Medicine, King's College London, London, United Kingdom.
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.affiliation: Faculty of Life Sciences &Medicine, King's College London, London, United Kingdom.
authors.forename: Maltina
authors.initials: M
authors.lastname: Shkodra
authors.affiliation: Faculty of Life Sciences &Medicine, King's College London, London, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Tena
authors.affiliation: King's College Hospital, King's College London, London, United Kingdom.
authors.forename: Parthi
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: King's College Hospital, King's College London, London, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Heaton
authors.affiliation: King's College Hospital, King's College London, London, United Kingdom.
authors.forename: Wayel
authors.initials: W
authors.lastname: Jassem
authors.affiliation: Faculty of Life Sciences &Medicine, King's College London, London, United Kingdom.
authors.forename: Cristina
authors.initials: C
authors.lastname: Legido-Quigley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064591:Allografts / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001926:Brain Death / Q000378:metabolism / Q000473:pathology; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012769:Shock / Q000378:metabolism / Q000401:mortality; D014019:Tissue Donors; D066027:Transplant Recipients; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D008246:Lysophospholipids