AB0056 Correlation between Serum Levels of IL-15 and IL-17 in Patients with Idiopathic Inflammatory Myopathies. (10th June 2014) - Notarnicola, A.
Abstract : Background: The pathogenesis of Idiopathic Inflammatory Myopathies (IIM), including Polymyositis (PM), Dermatomyositis (DM) and the specific phenotype called anti-synthetase syndrome (ASS), is not yet entirely understood. Recently, Interleukin-15 (IL-15) and IL-17 have emerged as candidate mediators of induction/expansion of the pro-inflammatory cytokine cascade in IIM, and systemic or muscle production of IL-15 and IL-17 has been demonstrated in patients affected by IIM [1–4]. Objectives: To assess the serum levels of IL-15 and IL-17 in patients with IIM and correlate them with IL-1 receptor antagonist (IL-1ra), IL-6, IL-10, interferon-gamma (IFNγ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β levels. Possible correlations with disease activity parameters were also evaluated. Methods: Sera from 14 PM, 10 DM, 7 ASS new onset patients and 19 healthy controls (HC) were analyzed by multiplex immunoassay. Sera from 19 patients were analyzed after 5 months median follow-up. All patients underwent physical examination, the 5-points Manual Muscle Test (MMT) [8], the Health Assessment Questionnaire (HAQ) and serum Creatine Kinase (CK) measurement. All patients received glucocorticoids, and 13 were taking immunosuppressive therapy. Results: At baseline, serum levels of IL-15, IL-17, MCP-1 and MIP-1β were significantly higher in IIM patients than in HC. IL-17 serum levels were directly correlated (r=0.39, p=0.02) with disease duration while a significant inverse correlation was detected between IL-17 levels and MMT scores (r=-0.4, p=0.02). The highest IL-15 levels were present in DM patients (p=0.02 vs PM). The most striking finding was the strong correlation between IL-15 and IL-17 levels (r=0.60, p=0.0001), and this correlation was even stronger in DM patients (r=0.82, p=0.006). Conclusions: The strong correlation between IL-15 and IL-17 in IIM patients, and especially in DM, suggests that there may be an interplay between the two cytokines in the pathogenesis of myositis. Further studies of larger patient cohorts and of muscle biopsies are needed to confirm these preliminary data. References: Zong M, Loell I, Lindroos E et al. Effects of immunosuppressive treatment on interleukin-15 and interleukin-15 receptor alpha expression in muscle tissue of patients with polymyositis or dermatomyositis. Ann Rheum Dis 71; 1055-63. Sugiura T, Harigai M, Kawaguchi Y et al. Increased IL-15 production of muscle cells in polymyositis and dermatomyositis. Int Immunol 14; 917-24. Tournadre A, Miossec P Interleukin-17 in inflammatory myopathies. Curr Rheumatol Rep 14; 252-6. Szodoray P, Alex P, Knowlton N et al. Idiopathic inflammatory myopathies, signified by distinctive peripheral cytokines, chemokines and the TNF family members B-cell activating factor and a proliferation inducing ligand. Rheumatology (Oxford) 49; 1867-77. Rider LG, Giannini EH, Harris-Love M et al. Defining Clinical Improvement in Adult and Juvenile Myositis. J Rheumatol 30; 603-17. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2014-eular.1053