AB0123\u2005CCL17 IN SYNOVIAL FLUID AND PLASMA OF PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

Abstract

Background Despite the advancements in management of rheumatoid arthritis (RA) in the last two decades, there are still a significant number of patients who cannot achieve low disease states or remission with the current available therapy. Granulocyte macrophage-colony stimulating factor (GM-CSF) is a key mediator in inflammation and autoimmunity, and has emerged as a novel therapeutic target in RA. However, potential adverse side effects warrant further investigation of a more specific target. Objectives Chemokine (C-C motif) ligand 17 (CCL17) is a downstream mediator of GM-CSF and has recently been shown to be regulated by GM-CSF in human monocytes. Significantly, CCL17 has a non-redundant role in inflammatory arthritis and pain. We investigated the expression levels of CCL17 in synovial fluid and plasma from RA patients. Methods We recruited RA patients with symptomatic swollen joints, who require joint aspiration for diagnostic and/or therapeutic purposes. Synovial fluid and plasma were collected and CCL17 protein levels were determined by ELISA. Results CCL17 protein was measured in synovial fluid and plasma samples from our cohort of RA patients. Levels of secreted CCL17 were higher in plasma [median 240 (40-580) pg/ml] compared to synovial fluid [median 100 (30-300) pg/ml] p<0.05. Conclusion Significant levels of CCL17 were detected in RA synovial fluid and plasma. This is a novel study which demonstrates and compares the presence of CCL17 in synovial fluid and plasma from matching RA patients. The expression of CCL17 in plasma can make it a useful potential biomarker for RA, while its expression in synovial fluid suggests that CCL17 may be a therapeutic target for treating RA. References [1] Gibofsky, A., Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A Synopsis. Am J Manag Care, 2014. 20(7Suppl): p. S128-35. [2] Hamilton, J.A., GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential. Expert Rev Clin Immunol, 2015. 11(4): p. 457-65. [3] Achuthan, A., et al., Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation. J Clin Invest, 2016. 126(9): p. 3453-66. Disclosure of Interests Cecil Hor Speakers bureau: Mundipharma, Pfizer, Adrian Achuthan: None declared, Keith Lim Consultant for: Advisor for role of hepatitis and TB in Cimzia, UCB, Speakers bureau: Role of biological in pregnancy UCB, John Hamilton Grant/research support from: GSK