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. 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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Disclosure of Interest None declared