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Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation

N M Wulffraat¹, P J Haas¹, M Frosch², I M de Kleer¹, T Vogl², D M C Brinkman³, P Quartier⁴, J Roth², W Kuis¹

¹ Department of Paediatric Immunology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, The Netherlands
² Department of Paediatrics and Institute of Experimental Dermatology, University of Münster, Germany
³ Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands
⁴ Department of Paediatric Immunology, Haematology and Rheumatology, Necker-Enfants Malades Hospital, Paris, France

Correspondence to:
Correspondence to:
Dr N M Wulffraat, Suite KC 03.063, University Medical Centre Utrecht, Department of Paediatric Immunology, Post Box 85090, zip 3508 AB Utrecht, The Netherlands;
N.Wulffraat{at}wkz.azu.nl

Objectives: To determine whether myeloid related proteins (MRP8/MRP14), a complex of two S100 proteins related to neutrophil and monocyte activation, might be used as a marker for disease activity, and as an early indicator of relapse in juvenile idiopathic arthritis.

Patients and methods: A group of 12 patients who underwent an autologous haematopoietic stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA) were studied. MRP8/MRP14 serum concentrations were determined by a sandwich enzyme linked immunosorbent assay (ELISA) as described. Improvement from baseline was described by a definition of improvement employing a core set of criteria as detailed previously by Giannini.

Results: After ASCT, MRP8/MRP14 serum concentrations in JIA showed a positive correlation with the Child Health Assessment Questionnaire (CHAQ; r=0.80) and erythrocyte sedimentation rate (r=0.45), but not with the total leucocyte count (r=0.26). Mean MRP8/MRP14 serum concentrations dropped markedly in the first three months after ASCT (p=0.0039) and clinical parameters of disease activity such as CHAQ markedly improved (p=0.0039). During a transient relapse there was an increase in MRP8/MRP14.

Conclusions: MRP8/MRP14 serum concentration can be used as a marker for disease activity in patients who receive an ASCT for refractory JIA. This indicates a role of macrophage activation in the pathogenesis of JIA. The occurrence of MAS in three patients in this study was not preceded by significant changes in MRP8/MRP14 concentration.

Keywords: myeloid related proteins; juvenile idiopathic arthritis; stem cells

Abbreviations: ASCT, autologous stem cell transplantation; CHAQ, Child Health Assessment Questionnaire; CK, creatine kinase; CRP, C reactive protein; DMARDs, disease modifying antirheumatic drugs; ELISA, enzyme linked immunosorbent assay; ESR, erythrocyte sedimentation rate; JIA, juvenile idiopathic arthritis; MAS, macrophage activation syndrome; MRP, myeloid related protein; MTX, methotrexate; SLE, systemic lupus erythematosus; TNF, tumour necrosis factor

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