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

Ann Rheum Dis. 2012 Jun;71(6):974-80. doi: 10.1136/annrheumdis-2011-200598. Epub 2012 Jan 20.

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / immunology*
  • Adolescent
  • Anti-Inflammatory Agents / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / immunology*
  • Biomarkers / blood
  • Calgranulin B / immunology*
  • Child
  • Child, Preschool
  • Drug Monitoring / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Male
  • Methotrexate / therapeutic use
  • Methylprednisolone / therapeutic use
  • Predictive Value of Tests
  • Recurrence
  • Risk Factors
  • Toll-Like Receptor 4 / immunology
  • Young Adult

Substances

  • ABCC11 protein, human
  • ATP-Binding Cassette Transporters
  • Anti-Inflammatory Agents
  • Antirheumatic Agents
  • Biomarkers
  • Calgranulin B
  • Interleukin 1 Receptor Antagonist Protein
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Methylprednisolone
  • Methotrexate