title: Markedly Increased High-Mobility Group Box 1 Protein in a Patient with Small-for-Size Syndrome.
abstract: Background. Small-for-size syndrome (SFSS) occurs in the presence of insufficient liver mass to maintain normal function after liver transplantation. Murine mortality following 85% hepatectomy can be reduced by the use of soluble receptor for advanced glycation end products (sRAGE) to scavenge damage-associated molecular patterns and prevent their engagement with membrane-bound RAGE. Aims. To explore serum levels of sRAGE, high-mobility group box-1 (HMGB1) protein, and other soluble inflammatory mediators in a fatal case of SFSS. Methods. Serum levels of HMGB1, sRAGE, IL-18, and other inflammatory mediators were measured by ELISA in a case of SFSS, and the results were compared with 8 patients with paracetamol-induced acute liver failure (ALF) and 6 healthy controls (HC). Results. HMGB1 levels were markedly higher in the SFSS patient (92.1 ng/mL) compared with the ALF patients (median (IQR) 11.4 (3.7-14.8) ng/mL) and HC (1.42 (1.38-1.56) ng/mL). In contrast, sRAGE levels were lower in the SFSS patient (1.88 ng/mL) compared with the ALF patients (3.53 (2.66-12.37) ng/mL) and were similar to HC levels (1.40 (1.23-1.89) ng/mL). Conclusion. These results suggest an imbalance between pro- and anti-inflammatory innate immune pathways in SFSS. Modulation of the HMGB1-RAGE axis may represent a future therapeutic avenue in this condition.
authors.affiliation: Gastroenterology Department, The James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK.
authors.forename: Darren G
authors.initials: DG
authors.lastname: Craig
authors.affiliation: Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lee
authors.affiliation: Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: E Anne
authors.initials: EA
authors.lastname: Pryde
authors.affiliation: Adult and Paediatric Liver Services, St James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: Ernest
authors.initials: E
authors.lastname: Hidalgo
authors.affiliation: Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.affiliation: Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wigmore
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Forbes
authors.affiliation: Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Simpson