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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
  1. N M Wulffraat1,
  2. P J Haas1,
  3. M Frosch2,
  4. I M de Kleer1,
  5. T Vogl2,
  6. D M C Brinkman3,
  7. P Quartier4,
  8. J Roth2,
  9. W Kuis1
  1. 1Department of Paediatric Immunology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, The Netherlands
  2. 2Department of Paediatrics and Institute of Experimental Dermatology, University of Münster, Germany
  3. 3Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands
  4. 4Department of Paediatric Immunology, Haematology and Rheumatology, Necker-Enfants Malades Hospital, Paris, France
  1. 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

Abstract

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.

  • myeloid related proteins
  • juvenile idiopathic arthritis
  • stem cells
  • 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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