FRI0050 Differential Expression of OPG/RANKL/TRAIL System in Rheumatoid Arthritis
Authors: S. Remuzgo-Martínez, F. Genre, R. Lόpez-Mejías, B. Ubilla, V. Mijares, T. Pina, A. Corrales, R. Blanco, J. Martín, J. Llorca, M.Ά. González-Gay
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Osteoprotegerin (OPG)/ receptor activator of nuclear factor-κB ligand (RANKL)/ tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) system is involved in the pathophysiology of rheumatoid arthritis (RA) [1–2]. Moreover, this system has been related to cardiovascular (CV) disease and, therefore, these molecules have been proposed as potential biomarkers of CV disease [3–4]. <h3>Objectives</h3> To evaluate for the first time the differential expression of OPG/RANKL/TRAIL system in RA patients, with and without ischemic heart disease (IHD), and healthy controls, in order to confirm the role of this system in the pathogenesis of RA, the clinical and demographic characteristics of RA patients, and CV disease, assessed by IHD. <h3>Methods</h3> <i>OPG</i>, <i>RANKL</i> and <i>TRAIL</i> messenger RNA (mRNA) expression was quantified by quantitative real-time PCR in peripheral blood from 26 RA patients (12 with and 14 without IHD) and 10 healthy controls. Correlation coefficients were also assessed between <i>OPG</i>, <i>RANKL</i> and <i>TRAIL</i> expression levels in RA patients and their clinical and demographic characteristics, as well as the influence of <i>OPG</i> expression on its ligands. <h3>Results</h3> While <i>OPG</i> and <i>OPG/TRAIL</i> ratio expression was significantly increased in RA patients compared to controls (fold change=1.79, p=0.01 and 2.07, p=0.03, respectively), <i>RANKL/OPG</i> ratio was significantly decreased (fold change=0.50, p=0.02). Additionally, <i>OPG</i> mRNA levels were associated with <i>OPG/TRAIL</i> ratio (r=0.75, p=0.0002) and inversely related to <i>RANKL/OPG</i> ratio (r=-0.70, p=0.0008) in RA. No significant differences were found between patients and controls in <i>RANKL</i> and <i>TRAIL</i> expression. Interestingly, <i>TRAIL</i> mRNA expression was significantly higher in RA patients with compared to those without IHD (fold change=1.46, p=0.03). Moreover, biologic disease-modifying antirheumatic drugs (DMARDs) significantly decreased <i>RANKL</i> expression in RA patients (r=-0.54, p=0.02). <h3>Conclusions</h3> Our study supports a key role for <i>OPG</i> in RA disease and <i>TRAIL</i> in IHD in RA patients. Furthermore, it highlights the important modulation of <i>RANKL</i> in RA patients treated with biologic DMARDs. <h3>References</h3> Geusens et al. Ther Adv Musculoskelet Dis 2012, 4(4):225–33; Neve et al. Clin Exp Med 2014, 14(2):115–20; Venuraju et al. J Am Coll Cardioll 2010, 55(19):2049–61; Bernardi et al. Curr Drug Targets 2012, 13(9):1215–21. <h3>Acknowledgement</h3> This study was supported by European Union FEDER funds and “Fondo de Investigaciόn Sanitaria” (grants PI12/00060 and PI15/00525) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from ISCIII (Health Ministry, Spain), and in part by grants from the European IMI BTCure Program. FG is a recipient of a Sara Borrell postdoctoral fellowship from the ISCIII at the Spanish Ministry of Health (Spain) (CD15/00095). RL-M and BU is supported by funds from the RETICS Program (RIER) (RD12/0009/0013). <h3>Disclosure of Interest</h3> None declared