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Updated: May 25, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
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
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.
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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