Markedly Increased High-Mobility Group Box 1 Protein in a Patient with Small-for-Size Syndrome

Author:

Craig Darren G.1,Lee Patricia2,Pryde E. Anne2,Hidalgo Ernest3,Hayes Peter C.2,Wigmore Stephen J.2,Forbes Stuart J.4,Simpson Kenneth J.2

Affiliation:

1. Gastroenterology Department, The James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK

2. Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK

3. Adult and Paediatric Liver Services, St James’s University Hospital, Leeds LS9 7TF, UK

4. MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK

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.

Funder

Chief Scientist Office

Publisher

Hindawi Limited

Subject

General Earth and Planetary Sciences,General Engineering,General Environmental Science

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