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

• Published in: Annals of the rheumatic diseases Vol. 71; no. 6; pp. 974 - 980
• Main Authors: Holzinger, Dirk, Frosch, Michael, Kastrup, Astrid, Prince, Femke H M, Otten, Marieke H, Van Suijlekom-Smit, Lisette W A, Cate, Rebecca ten, Hoppenreijs, Esther P A H, Hansmann, Sandra, Moncrieffe, Halima, Ursu, Simona, Wedderburn, Lucy R, Roth, Johannes, Foell, Dirk, Wittkowski, Helmut
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2012; BMJ Publishing Group; Elsevier Limited
• Subjects: Adolescent; Anti-Inflammatory Agents - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Juvenile - blood; Arthritis, Juvenile - drug therapy; Arthritis, Juvenile - immunology; ATP-Binding Cassette Transporters - immunology; Biological and medical sciences; Biomarkers; Biomarkers - blood; C-reactive protein; Calgranulin B - immunology; Child; Child, Preschool; Children; Cytokines; Diseases of the osteoarticular system; Drug Monitoring - methods; Drugs; Enzyme-linked immunosorbent assay; Erythrocytes; Family medical history; Female; Fever; Follow-Up Studies; Health risk assessment; Humans; Inflammation; Inflammatory joint diseases; Interleukin 1; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Inventories; Joint diseases; Male; Medical sciences; Methotrexate; Methotrexate - therapeutic use; Methylprednisolone - therapeutic use; Pathogenesis; Patients; Predictive Value of Tests; Proteins; Recurrence; Remission; Risk Factors; Sedimentation; Serum levels; TLR4 protein; Toll-Like Receptor 4 - immunology; Toll-like receptors; Young Adult; Agonist; Relapse; Toll like receptor 4; Activity index; Diseases of the osteoarticular system; Rheumatology; Juvenile rheumatoid arthritis; Inflammatory joint disease; Protein A; Indicator; Chronic; Disseminated; Predictive factor
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2011-200598

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.