Article Text

OP0097 Systemic ifn type i and type ii signatures in primary sjÖgren's syndrome reveal differences in disease severity
  1. I Bodewes1,
  2. S Al-Ali2,3,
  3. CG van Helden1,
  4. NI Maria1,
  5. J Tarn2,
  6. D Lendrem2,
  7. MW Schreurs1,
  8. EC Steenwijk1,
  9. PLA van Daele1,4,
  10. T Both4,
  11. S Bowman5,
  12. B Griffiths6,
  13. W-F Ng2,7,
  14. MA Versnel1
  1. 1Immunology, Erasmus MC, Rotterdam, Netherlands
  2. 2Musculoskeletal Research group, Newcastle University, Newcastle upon Tyne, United Kingdom
  3. 3University of Basrah, Basrah, Iraq
  4. 4Internal Medicine, Erasmus MC, Rotterdam, Netherlands
  5. 5Rheumatology, University Hospital Birmingham, Birmingham
  6. 6Newcastle upon Tyne Hospitals NHS Foundation Trust
  7. 7National Institute for Health Research, Newcastle Biomedical Research Centre, Newcastle upon Tyne, United Kingdom


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.


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  2. Gottenberg, et al. PNAS. 2006; 103(8):2770–2775.

  3. Hjelmervik, et al. A&R. 2005; 52(5):1534–1544.

  4. Emamian, et al. Genes Immun. 2009; 10(4):285–296.

  5. Brkic, et al. ARD. 2013; 72(5):728–735.

  6. Hall, et al. PNAS. 2013; 72(5):728–735.

  7. Hall, et al. A&R. 2012; 109(43):17609–17614.


Disclosure of Interest None declared

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