title: Soluble receptor for advanced glycation endproducts is decreased in patients with juvenile idiopathic arthritis (ERA category) and inversely correlates with disease activity and S100A12 levels.
abstract: OBJECTIVE
  Membrane-bound receptor for advanced glycation endproducts (mRAGE) is overexpressed in response to increasing concentrations of its ligand (e.g., S100A12) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Decreased sRAGE levels are associated with autoimmune diseases; however, limited data are available in juvenile idiopathic arthritis (JIA). We studied sRAGE levels in patients with JIA [enthesitis-related arthritis (ERA) category].
  
  
  METHODS
  sRAGE levels were estimated in the serum of patients with ERA JIA (n = 101), systemic-onset JIA and polyarticular JIA (n = 10 each), and healthy controls (n = 45). Synovial fluid (SF) sRAGE was measured in patients with ERA, rheumatoid arthritis, reactive arthritis, and osteoarthritis (n = 10). Levels of S100A12 were also measured. Twenty-four patients with ERA were followed for 4 months. Disease activity was assessed by swollen joint count (SJC), tender joint count (TJC), and erythrocyte sedimentation rate (ESR). All levels are expressed as median (range).
  
  
  RESULTS
  The serum sRAGE (pg/ml) level was significantly lower in patients compared to healthy controls [515 (64-1887) vs 1542 (627-3159); p < 0.0001]. In paired samples, SF had lower levels compared to corresponding plasma level [102 (51-799) vs 481 (134-1006); p < 0.0001]. The level of S100A12 (ng/ml) was higher in SF (1042; 573-1415) than serum (638; 208-779). Serum sRAGE correlated negatively with S100A12 levels (r = -0.474; p < 0.01.), ESR (r = -0.306; p < 0.01), and SJC (r = -0.237; p < 0.05), but not with TJC (r = -0.134; p = NS). The levels of sRAGE remained stable over time in patients with stable disease.
  
  
  CONCLUSIONS
  Levels of sRAGE are reduced in patients with ERA and correlate negatively with disease activity and S100A12 levels. sRAGE may be a modulator of inflammation in these patients.
authors: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Arpita
authors: A
authors: Myles
authors: Vishad
authors: V
authors: Viswanath
authors: Yogesh Preet
authors: YP
authors: Singh
authors: Amita
authors: A
authors: Aggarwal
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000097:blood* / Q000276:immunology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology; D008297:Male; D011237:Predictive Value of Tests; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000502:physiology; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human