Imbalance of type I and II interferon pathways is associated with pain perception in Sjogren's disease: a real-life study.

Introduction: Activation of interferon (IFN) pathways is a central mechanism in the pathogenesis of Sjögren's disease (SjD) and systemic lupus erythematosus (SLE). While type I IFN signatures have been extensively characterized, the systemic relevance of circulating type III IFNs and the clinical implications of the relative balance between IFN types I, II, and III remain insufficiently explored. Methods: In this real-life, exploratory study, plasma concentrations of IFN-α2, IFN-β, IFN-γ, IFN-λ1, and IFN-λ2 were measured in patients with SjD (n = 59), SLE (n = 35), and healthy controls (n = 30). Disease activity and patient-reported outcomes were assessed using ESSDAI, ESSPRI, and SLEDAI-2K. In addition to absolute IFN concentrations, ratios between IFN subtypes were analyzed to reflect interferon pathway balance. Non-parametric statistical analyses with correction for multiple testing were applied. Results: Absolute plasma concentrations of individual IFN subtypes did not differ significantly between the study groups. In SjD, exploratory correlation analyses revealed a significant association between the IFN-α2/IFN-γ ratio and pain severity assessed by ESSPRI (Spearman's ρ = 0.48, adjusted Conclusions: These findings indicate that the relative balance between interferon pathways, rather than absolute circulating IFN levels, may be clinically relevant in SjD, particularly with respect to patient-reported pain. Interferon subtype ratios may represent exploratory biomarkers of immune dysregulation. Further studies integrating systemic, tissue-level, and transcriptomic approaches are warranted to validate these observations.