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Open Access Research article

Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis

Kiran Nistala1, Hemlata Varsani1, Helmut Wittkowski3, Thomas Vogl2, Petra Krol4, Vanita Shah1, Kamel Mamchaoui5, Paul A Brogan1, Johannes Roth2 and Lucy R Wedderburn1*

Author Affiliations

1 Rheumatology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK

2 Institute of Immunology and Interdisciplinary Centre for Clinical Research IZKF, University of Muenster, Muenster, Germany

3 Department of General Pediatrics, University Children’s Hospital Muenster, Muenster, Germany

4 Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 2, 12000 Prague 2, Czech Republic

5 Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6/U974 - Inserm/UMR7215 – CNRS, 47, bld de l’hôpital - G.H. Pitié-Salpétrière - Bâtiment Babinski, 75651 Paris, cedex 13, France

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Arthritis Research & Therapy 2013, 15:R131  doi:10.1186/ar4311

Published: 23 September 2013

Abstract

Introduction

The aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly understood. In particular the contribution of monocytes or macrophages, which are frequently observed to be an infiltrate within muscle tissue very early in the disease process, is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to muscle pathology in JDM.

Methods

In this study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of disease activity. Muscle biopsies taken early in disease were assessed by immunohistochemistry to determine the frequency and identity of MRP-expressing cells. The effects of MRP stimulation and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analyzed by multiplex immunoassay.

Results

Serum MRP8/14 correlated with physician’s global assessment of disease activity in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis assessment score (CMAS, R = −0.55, p = 0.004). MRP8/14 was widely expressed by CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8 led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both inflammatory mediators were detected in significantly higher levels in the serum of JDM patients compared to healthy controls.

Conclusions

This study is the first to identify serum MRP8/14 as a potential biomarker for disease activity in JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may contribute to myositis, by driving the local production of cytokines directly from muscle.