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AB0164 Analysis of Jak-Stat-Socs Signal Pathway MRNA Expression in Ankylosing Spondylitis (AS) Patients with Peripheral Arthritis (PA)
  1. M.A. Sánchez1,
  2. R. Villares2,
  3. J. Campos1,
  4. P. Lucas2,
  5. J. Rodríguez-Frade2,
  6. J. Sanz1,
  7. C. Fernández-Espartero3,
  8. T. Clavaguera4,
  9. C. Méndez1,
  10. C. Sanguesa1,
  11. B.J. Flores1,
  12. E. Collantes-Estévez5,
  13. M. Mellado2,
  14. J. Mulero1
  1. 1Rheumatology, Hospital Universitario Puerta de Hierro Majadahonda
  2. 2Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC)
  3. 3Rheumatology, Hospital Universitario Mόstoles, Madrid
  4. 4Rheumatology, Hospital de Palamόs, Girona
  5. 5Rheumatology, Hospital Universitario Reina Sofía, Cόrdoba, Spain

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

  1. 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

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