The presence of high mobility group box-1 and soluble receptor for advanced glycation end-products in juvenile idiopathic arthritis and juvenile systemic lupus erythematosus.

Marija Jelušić,Danka Grčević,Dubravka Bobek,Ivan Krešimir Lukić,Nataša Kovačić

doi:10.1186/1546-0096-12-50

Abstract

BackgroundThe involvement of high mobility group box-1 (HMGB1) in various inflammatory and autoimmune diseases has been documented but clinical trials on the contribution of this pro-inflammatory alarmin in children with juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) are basically absent. To address the presence of HMGB1 and a soluble receptor for advanced glycation end products (sRAGE) in different subtypes of JIA and additionally in children with SLE, we enrolled a consecutive sample of children harvested peripheral blood as well as synovial fluids (SF) at diagnosis and correlated it with ordinary acute-phase reactants and clinical markers.MethodsSerum and synovial fluids levels of HMGB1 and sRAGE in total of 144 children (97 with JIA, 19 with SLE and 27 healthy controls) were determined by ELISA.ResultsThe children with JIA and those with SLE were characterised by significantly higher serum levels of HMGB1 and significantly lower sRAGE levels compared to the healthy controls. A positive correlation between serum HMGB1 and ESR, CRP, α2 globulin was found while serum sRAGE levels were inversely correlated with the same inflammatory markers in children with JIA. Additionally, high level of serum HMGB1 was related to hepatosplenomegaly or serositis in systemic onset JIA.ConclusionThe inverse relationship of the HMGB1 and its soluble receptor RAGE in the blood and SF indicates that inflammation triggered by alarmins may play a role in pathogenesis of JIA as well as SLE. HMGB1 may serve as an inflammatory marker and a potential target of biological therapy in these patients. Further studies need to show whether the determination of HMGB1 levels in patients with JIA can be a useful guideline for detecting disease activity.

Highlights

The involvement of high mobility group box-1 (HMGB1) in various inflammatory and autoimmune diseases has been documented but clinical trials on the contribution of this pro-inflammatory alarmin in children with juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) are basically absent
The following routine laboratory tests were performed at the Department of Clinical Laboratory Diagnostics, University of Zagreb School of Medicine: erythrocyte sedimentation rate (ESR; mm/hour), C-reactive protein levels (CRP; mg/l), α2globulins (%), γ-globulins (%), white blood cells count (WBC; ×10^9/l), red blood cells (RBC; ×10^12/l), platelets (PLT; ×10^9/l), hemoglobin (g/l), haematocrit (%)
All the patients with systemic-onset JIA presented with spiking fevers and skin rash as well as high ESR, CRP and α2-globulins

Summary

Introduction

The involvement of high mobility group box-1 (HMGB1) in various inflammatory and autoimmune diseases has been documented but clinical trials on the contribution of this pro-inflammatory alarmin in children with juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) are basically absent. Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritis diseases with the onset before 16 years of age and persistent for more than 6 weeks. At the initial presentation of sJIA, arthritis may not be present. In the field of pediatrics, in addition to sJIA, there is childhood SLE (cSLE) – is another acute inflammatory disorder frequently presenting a diagnostic and therapeutic challenge. CSLE is a complex autoimmune inflammatory disease characterized by multiorgan involvement. 20% of SLE cases begin before age 19 and often have a poor prognosis [3]

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