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

Darren G Craig,Stuart J Forbes,Ernest Hidalgo,E Anne Pryde,Peter C Hayes,Patricia Lee,Stephen J Wigmore,Kenneth J Simpson

doi:10.1155/2014/272498

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.

Highlights

The capacity for liver regeneration is finite, placing a restriction upon the minimum mass of liver tissue required to maintain hepatic function following split liver transplantation (LT) or liver resection
SRAGE levels were lower in the Small-for-size syndrome (SFSS) patient (1.88 ng/mL) compared with the paracetamol overdose patients (3.53 (2.66–12.37) ng/mL, n = 8) and were similar to healthy controls (1.40 (1.23–1.89) ng/mL, n = 6)
This study suggests that an imbalance in the high-mobility group box-1 (HMGB1)-receptor for advanced glycation end products (RAGE) axis may be involved in the pathogenesis of SFSS

Summary

Introduction

The capacity for liver regeneration is finite, placing a restriction upon the minimum mass of liver tissue required to maintain hepatic function following split liver transplantation (LT) or liver resection. Engagement of membrane-bound RAGE with ligands such as high-mobility group box 1 (HMGB1) protein sustains inflammatory responses and promotes apoptosis in the hepatic remnant following massive hepatectomy [4]. 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. To explore serum levels of sRAGE, high-mobility group box-1 (HMGB1) protein, and other soluble inflammatory mediators in a fatal case of SFSS. 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). Modulation of the HMGB1-RAGE axis may represent a future therapeutic avenue in this condition

Methods

Results

Conclusion