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Rheumatoid arthritis - etiology, pathogenesis and animal models
FRI0050 Differential Expression of OPG/RANKL/TRAIL System in Rheumatoid Arthritis
  1. S. Remuzgo-Martínez1,
  2. F. Genre1,
  3. R. Lόpez-Mejías1,
  4. B. Ubilla1,
  5. V. Mijares1,
  6. T. Pina1,
  7. A. Corrales1,
  8. R. Blanco1,
  9. J. Martín2,
  10. J. Llorca3,
  11. M.Ά. González-Gay1,4,5
  1. 1Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Department, IDIVAL, Santander
  2. 2Institute of Parasitology and Biomedicine Lόpez-Neyra, IPBLN-CSIC, Granada
  3. 3Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiology and Public Health (CIBERESP), IDIVAL, Santander, Spain
  4. 4Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  5. 5School of Medicine, University of Cantabria, Santander, Spain

Abstract

Background 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].

Objectives 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.

Methods OPG, RANKL and TRAIL 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 OPG, RANKL and TRAIL expression levels in RA patients and their clinical and demographic characteristics, as well as the influence of OPG expression on its ligands.

Results While OPG and OPG/TRAIL 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), RANKL/OPG ratio was significantly decreased (fold change=0.50, p=0.02). Additionally, OPG mRNA levels were associated with OPG/TRAIL ratio (r=0.75, p=0.0002) and inversely related to RANKL/OPG ratio (r=-0.70, p=0.0008) in RA. No significant differences were found between patients and controls in RANKL and TRAIL expression. Interestingly, TRAIL 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 RANKL expression in RA patients (r=-0.54, p=0.02).

Conclusions Our study supports a key role for OPG in RA disease and TRAIL in IHD in RA patients. Furthermore, it highlights the important modulation of RANKL in RA patients treated with biologic DMARDs.

  1. Geusens et al. Ther Adv Musculoskelet Dis 2012, 4(4):225–33;

  2. Neve et al. Clin Exp Med 2014, 14(2):115–20;

  3. Venuraju et al. J Am Coll Cardioll 2010, 55(19):2049–61;

  4. Bernardi et al. Curr Drug Targets 2012, 13(9):1215–21.

Acknowledgement 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).

Disclosure of Interest None declared

https://doi.org/10.1136/annrheumdis-2016-eular.2702

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