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Abstract Number: 1674

Myeloid Related Proteins Induce Muscle Derived Inflammatory Mediators in Juvenile Dermatomyositis

Kiran Nistala1, Hemlata Varsani2, Helmut Wittkowski3, Thomas Vogl4, Petra Krol5, Vanita Shah2, Kamel Mamchaoui6, Paul Brogan2, Johannes Roth7 and Lucy R. Wedderburn2, 1Paediatric Rheumatology International Trials Organization (PRINTO), Genova, Italy, 2Rheumatology Unit , Institute of Child Health, University College London (UCL), London, United Kingdom, 3Muenster, Germany, 4Institute of Immunology, University of Muenster, Muenster, Germany, 5Rheumatology Unit, Department of Paediatrics and Adolescent Medicine, Prague, Czech Republic, 6Institut de Myologie, Paris, France, 7Immunology, Institute of Immunology University of Muenster, Muenster, Germany

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: chemokines, interleukins (IL), Juvenile dermatomyositis and myositis

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Session Information

Title: Muscle Biology, Myositis and Myopathies: Pathogenesis in Idiopathic Inflammatory Myopathies

Session Type: Abstract Submissions (ACR)

Background/Purpose: The etiopathogenesis 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 S100 proteins myeloid related peptide (MRP)-8/14 which may then contribute to muscle pathology in JDM.

Methods: In this study of 75 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 ER stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analysed by multiplex immunoassay.

Results: Serum MRP8/14 correlated with physician’s global assessment of disease activity in JDM (r2=0.26, p=0.006), functional assessment (CHAQ, r2=0.31, p=0.0498), and strength/stamina (CMAS, r2=0.28, p=0.028). 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.

Conclusion: This study is the first to identify serum MRP8/14 as a 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.


Disclosure:

K. Nistala,
None;

H. Varsani,
None;

H. Wittkowski,
None;

T. Vogl,
None;

P. Krol,
None;

V. Shah,
None;

K. Mamchaoui,
None;

P. Brogan,
None;

J. Roth,
None;

L. R. Wedderburn,
None.

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