title: 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.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  Serum 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Pediatrics, Division of Pediatric Rheumatology and Immunology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Kišpatićeva 12, 10000 Zagreb, Croatia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Bobek
authors.affiliation: Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Danka
authors.initials: D
authors.lastname: Grčević
authors.affiliation: Department of Anatomy, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Kovačić
authors.affiliation: Department of Research in Biomedicine, and Health, University of Split School of Medicine, Split, Croatia.
authors.forename: Ivan Krešimir
authors.initials: IK
authors.lastname: Lukić
authors.affiliation: Department of Pediatrics, Division of Pediatric Rheumatology and Immunology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Kišpatićeva 12, 10000 Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Jelušić
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000175:diagnosis* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000378:metabolism*; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D002097:C-Reactive Protein
keywords: High mobility group box-1; Juvenile idiopathic arthritis; Juvenile systemic lupus erythematosus; Solubile receptor for advanced glycation end-products