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

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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