title: The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis.
abstract: BACKGROUND
  Analysis of myeloid-related protein 8 and 14 complex (MRP8/14) serum concentrations is a potential new tool to support the diagnosis of systemic-onset juvenile idiopathic arthritis (SJIA) in the presence of fever of unknown origin.
  
  
  OBJECTIVE
  To test the ability of MRP8/14 serum concentrations to monitor disease activity in patients with SJIA and stratify patients at risk of relapse.
  
  
  METHODS
  Serum concentrations of MRP8/14 in 52 patients with SJIA were determined by a sandwich ELISA. The monitoring of therapeutic regimens targeting interleukin 1 and tumour necrosis factor α, and methotrexate treatment was analysed and diagnostic power to predict flares was tested.
  
  
  RESULTS
  MRP8/14 levels were clearly raised in active disease and decreased significantly in response to successful treatments. Serum concentrations of MRP8/14 increased significantly (p<0.001) (mean±95% CI 12.030±3.090 ng/ml) during disease flares compared with patients with inactive disease (864±86 ng/ml). During clinical remission MRP8/14 serum levels of >740 ng/ml predicted disease flares accurately (sensitivity 92%, specificity 88%). MRP8/14 levels correlated well with clinical disease activity, as assessed by physician's global assessment of disease activity (r=0.62), Childhood Health Assessment Questionnaire (r=0.56), active joint count (r=0.46) and with C-reactive protein (r=0.71) and erythrocyte sedimentation rate (r=0.72) (for all p<0.001).
  
  
  CONCLUSIONS
  MRP8/14 serum concentrations correlate closely with response to drug treatment and disease activity and therefore might be an additional measurement for monitoring anti-inflammatory treatment of individual patients with SJIA. MRP8/14 serum concentrations are the first predictive biomarker indicating subclinical disease activity and stratifying patients at risk of relapse during times of clinically inactive disease.
authors.affiliation: Institute of Immunology, University Hospital Muenster, Muenster, Germany. dirk.holzinger@ukmuenster.de
authors.forename: Dirk
authors.initials: D
authors.lastname: Holzinger
authors.forename: Michael
authors.initials: M
authors.lastname: Frosch
authors.forename: Astrid
authors.initials: A
authors.lastname: Kastrup
authors.forename: Femke H M
authors.initials: FH
authors.lastname: Prince
authors.forename: Marieke H
authors.initials: MH
authors.lastname: Otten
authors.forename: Lisette W A
authors.initials: LW
authors.lastname: Van Suijlekom-Smit
authors.forename: Rebecca
authors.initials: R
authors.lastname: ten Cate
authors.forename: Esther P A H
authors.initials: EP
authors.lastname: Hoppenreijs
authors.forename: Sandra
authors.initials: S
authors.lastname: Hansmann
authors.forename: Halima
authors.initials: H
authors.lastname: Moncrieffe
authors.forename: Simona
authors.initials: S
authors.lastname: Ursu
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
authors.forename: Helmut
authors.initials: H
authors.lastname: Wittkowski
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D040502:Calgranulin B / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008775:Methylprednisolone / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012008:Recurrence; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000276:immunology; D055815:Young Adult
chemical_list: C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D015415:Biomarkers; D040502:Calgranulin B; D053590:Interleukin 1 Receptor Antagonist Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D008775:Methylprednisolone; D008727:Methotrexate