title: Circulating keratan sulfate as a marker of metabolic changes of cartilage proteoglycan in juvenile idiopathic arthritis; influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations.
abstract: BACKGROUND
  The aim of this study was to evaluate the plasma keratan sulfate (KS) level as a potential marker of joint damage in children with juvenile idiopathic arthritis (JIA). The influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations were evaluated in this study.
  
  
  METHODS
  Plasma levels of KS, transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS-4 and ADAMTS-5), and thiol groups (TG) were quantified in samples obtained from 30 healthy subjects and 30 patients with JIA before and after treatment.
  
  
  RESULTS
  Increased (p<0.01) plasma KS was observed in JIA patients before treatment. Therapy resulted in a decrease in KS level. However, plasma KS level remained higher (p<0.05) than in controls. Increased levels of TGF-β1 (p<0.01) and PDGF-BB (p<0.05) in untreated JIA patients were recorded. Clinical improvement was accompanied by significant decrease in TGF-β1 and PDGF-BB, compared with a pretreatment condition and a control group. The concentrations of proteinases were characterized by different trends of alterations. When the ADAMTS-4 level increased (p<0.01) in the blood of untreated patients, the concentration of ADAMTS-5 was found to be reduced (p<0.0001), compared with controls. JIA treatment resulted in the normalization of ADAMTS-4 level. Plasma TG concentration was decreased only in untreated patients (p<0.05). We have revealed a significant correlation between plasma KS level and ADAMTS-4, TGF-β1, TG, C-reactive protein, and erythrocyte sedimentation rate levels.
  
  
  CONCLUSIONS
  Plasma KS level in JIA patients, reflecting the aggrecan structure, indicates that treatment that modifies inflammation simultaneously does not contribute to total regeneration of articular matrix components and signalizes the need for further treatment.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Winsz-Szczotka
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Komosińska-Vassev
authors.forename: Kornelia
authors.initials: K
authors.lastname: Kuźnik-Trocha
authors.forename: Andrzej
authors.initials: A
authors.lastname: Siwiec
authors.forename: Bogusław
authors.initials: B
authors.lastname: Żegleń
authors.forename: Krystyna
authors.initials: K
authors.lastname: Olczyk
mesh_terms: D000293:Adolescent; D053674:Aggrecans / Q000097:blood / Q000378:metabolism*; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D000077214:Becaplermin; D015415:Biomarkers / Q000097:blood; D002356:Cartilage / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D007632:Keratan Sulfate / Q000097:blood*; D008297:Male; D011509:Proteoglycans / Q000378:metabolism*; D059748:Proteolysis; D020574:Proto-Oncogene Proteins c-sis / Q000097:blood / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism*
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D011509:Proteoglycans; D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D007632:Keratan Sulfate