AB0164 Analysis of Jak-Stat-Socs Signal Pathway MRNA Expression in Ankylosing Spondylitis (AS) Patients with Peripheral Arthritis (PA)
Authors: M.A. Sánchez, R. Villares, J. Campos, P. Lucas, J. Rodríguez-Frade, J. Sanz, C. Fernández-Espartero, T. Clavaguera, C. Méndez, C. Sanguesa, B.J. Flores, E. Collantes-Estévez, M. Mellado, J. Mulero
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> 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.<sup>1</sup> <h3>Objectives</h3> 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. <h3>Methods</h3> 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 Student9s <i>t-</i> test. P-values of &lt;0.05 were considered statistically significant. <h3>Results</h3> Patients with AS and PA showed lower expressions levels of SOCS-1 (<i>P</i>=0,05), SOCS-2 (<i>P</i>=0,04) and especially of SOCS3 (<i>P</i>=0,002) as well as higher expression levels of JAK2 (<i>P</i>=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 (<i>P</i>=0,02). Besides we found a trend that didn9t reach statistical significance in these patients carrying the protective allele C, so that they showed higher levels of SOCS transcripts, especially of SOCS-3 (<i>P</i>=0.1). <h3>Conclusions</h3> 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. <h3>References</h3> Ann Rheum Dis 2011;70(Suppl3):215. <h3>Acknowledgements</h3> 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. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2496