AB0164 Analysis of Jak-Stat-Socs Signal Pathway MRNA Expression in Ankylosing Spondylitis (AS) Patients with Peripheral Arthritis (PA). (10th June 2014)

• Record Type: Journal Article
• Authors: Sánchez, M.A.; Villares, R.; Campos, J.; Lucas, P.; Rodríguez-Frade, J.; Sanz, J.; Fernández-Espartero, C.; Clavaguera, T.; Méndez, C.; Sanguesa, C.; Flores, B.J.; Collantes-Estévez, E.; Mellado, M.; Mulero, J.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 857
• Page End: 857
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.2496
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Cytokines play a key pathogenic role in Ankylosing Spondylitis (AS). Several cytokines, such as IL-23, signal through the JAK-STAT pathway, which is negatively regulated by the suppressors of cytokine signalling (SOCS) proteins. In a previous study our group found a significant association between the intronic polymorphism rs7857730 in JAK2 gene and the presence of peripheral arthritis at disease onset in AS patients. 1 Objectives: The aim of this study is to assess the gene expression of JAK2 and SOCS-1, -2 -3 in peripheral blood mononuclear cells (PBMCs) in relation with the presence of PA as well as in relation with the intronic polymorphism rs7857730 of JAK2. Methods: We studied 26 patients (19 males and 7 females) recruited from the National Spondyloarthropathies Registry (REGISPONSER) diagnosed of AS following the Modified New York Criteria. The study cohort included patients with a mean age of 58.5±8.0 years. The 30.7% of the patients had peripheral arthritis. Total RNA was extracted from PBMCs using the Nucleospin RNA kit (MN) and reverse transcribed into cDNA. mRNA expression was assessed by real-time quantitative RT-PCR using specific primers and Power SYBRGreen PCR Master Mix (Applied Biosystems) in the case of SOCS-1, -2 -3 or with RealTime Ready probes (Roche) for JAK2 expression. The results and statistical analysis were processed with Microsoft Excel, and SPSS v 15.0 softwares using the unpaired Student's t- test. P-values of <0.05 were considered statistically significant. Results: Patients with AS and PA showed lower expressions levels of SOCS-1 ( P =0, 05), SOCS-2 ( P =0, 04) and especially of SOCS3 ( P =0, 002) as well as higher expression levels of JAK2 ( P =0, 02) than patients without PA. Regarding the JAK2 rs7857730 polymorphism, we observed an increased expression of this transcript in patients homozygous for the PA risk allele A compared with C carriers ( P =0, 02). Besides we found a trend that didn't reach statistical significance in these patients carrying the protective allele C, so that they showed higher levels of SOCS transcripts, especially of SOCS-3 ( P =0.1). Conclusions: Our study confirms that the patients with AS and PA at disease onset had a higher expression levels of JAK2, as well as a lower expression levels of SOCS transcripts. These differences could lead to an increased cell activation in response to cytokines suchs as IL-23, because of the higher presence of activator proteins and lower expression of inhibitory proteins, which could be related to the clinical manifestation of PA in these AS patients. References: Ann Rheum Dis 2011;70(Suppl3):215. Acknowledgements: This work have been supported by Fondo de Investigaciones Sanitarias (PI11/00400) and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+I 2008-2011, (FEDER). We are grateful to all the patients who have participated in the study. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2014-eular.2496