The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts

Dirk Holzinger1, Michael Frosch, Astrid Kastrup

  • 1Institute of Immunology, University Hospital Muenster, Muenster, Germany. dirk.holzinger@ukmuenster.de

Abstract

Insights

Myeloid-related protein 8/14 (MRP8/14) serum levels effectively monitor systemic-onset juvenile idiopathic arthritis (SJIA) activity. Elevated MRP8/14 during remission accurately predicts disease flares, aiding in relapse risk stratification.

Area of Science:

  • Rheumatology
  • Immunology
  • Biomarker Discovery

Background:

  • Systemic-onset juvenile idiopathic arthritis (SJIA) diagnosis can be challenging, particularly with fever of unknown origin.
  • Myeloid-related protein 8 and 14 complex (MRP8/14) serum concentrations show potential as a diagnostic and monitoring tool for SJIA.

Purpose of the Study:

  • To evaluate the utility of MRP8/14 serum concentrations in monitoring SJIA disease activity.
  • To assess the ability of MRP8/14 to stratify patients at risk of disease relapse.

Main Methods:

  • Serum MRP8/14 concentrations were measured using a sandwich ELISA in 52 SJIA patients.
  • Therapeutic responses to IL-1, TNF-α inhibitors, and methotrexate were analyzed.
  • The diagnostic power of MRP8/14 for predicting disease flares was tested.

Main Results:

  • MRP8/14 levels were significantly elevated in active SJIA and decreased with effective treatment.
  • Serum MRP8/14 concentrations increased significantly during disease flares compared to inactive disease (p<0.001).
  • MRP8/14 levels (>740 ng/ml) during remission accurately predicted flares (92% sensitivity, 88% specificity) and correlated with clinical activity and inflammatory markers (p<0.001).

Conclusions:

  • MRP8/14 serum concentrations closely reflect treatment response and disease activity in SJIA.
  • MRP8/14 may serve as an additional biomarker for monitoring anti-inflammatory treatment in SJIA patients.
  • MRP8/14 is the first predictive biomarker for subclinical disease activity and relapse risk in clinically inactive SJIA.

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