OP0097 Systemic ifn type i and type ii signatures in primary sjÖgren's syndrome reveal differences in disease severity. (15th June 2017)

• Record Type: Journal Article
• Authors: Bodewes, I; Al-Ali, S; Helden, CG van; Maria, NI; Tarn, J; Lendrem, D; Schreurs, MW; Steenwijk, EC; Daele, PLA van; Both, T; Bowman, S; Griffiths, B; Ng, W-F; Versnel, MA
• Is Part Of: Annals of the rheumatic diseases. Volume 76(2017)Supplement 2
• Page Start: 92
• Page End: 92
• Publication Date: 2017-06-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-eular.3688
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Local and systemic activation of interferons (IFNs) has been demonstrated in primary Sjögren's syndrome (pSS).[1–4] Type I IFNs are associated with higher disease activity and autoantibody levels.[5] Recent findings also show activation of interferon type II (IFNγ) induced gene expression in salivary glands of pSS patients.[6, 7] Although IFN type I and II bind to different receptors they induce partially overlapping gene expression patterns. Understanding the relative contribution of IFN type I and type II may deepen our knowledge in pSS pathogenesis and promote a stratified approach to therapeutic development. Objectives: Determine IFN type I and II inducible gene expression in patients with pSS and correlate this to disease manifestations. Methods: In whole blood of 50 pSS patients modular IFN scores were determined using real-time quantitative PCR followed by principal component analysis. Subsequently, five indicator genes per module were analysed in two independent European cohorts with a total of 141 patients. Results: Three groups were distinguished: without IFN activation (19–47%), with IFN type I (53–81%) and with IFN type I+II activation (35–55%). Patients with IFN activation (I or I+II) have a higher presence of auto-antibodies, IgG levels and lower lymphocyte counts compared to IFN negative patients. The biological domain of the EULAR Sjögren's Syndrome Disease Activity Index (biological-ESSDAI) was higher in patients with IFN activation, while total-ESSDAI scores were not significantly different. 66–67% of the IFN type I positive patients had an additional IFN type II inducible gene expression. Patients with IFN type I+II activation have significantly higher IgG levels and lower lymphocyte counts compared to patients with only IFN type I activation. There were no differences in fatigue or dryness, but pain scores were lower. Conclusions: pSS patients can be stratified according to their systemic IFN activation patterns. IFN activation (I or I+II) is present in patients with the highest activity of the biological-ESSDAI. These data raise the possibility that the biological-ESSDAI rather than total-ESSDAI score may be a more sensitive endpoint for trials targeting either type I or type II IFN pathways. References: Wildenberg, et al. EJI. 2008; 38(7):2024–2033. Gottenberg, et al. PNAS. 2006; 103(8):2770–2775. Hjelmervik, et al. A&R. 2005; 52(5):1534–1544. Emamian, et al. Genes Immun. 2009; 10(4):285–296. Brkic, et al. ARD. 2013; 72(5):728–735. Hall, et al. PNAS. 2013; 72(5):728–735. Hall, et al. A&R. 2012; 109(43):17609–17614. Disclosure of Interest: None declared