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Three Sjögren's disease (SjD) patient clusters show distinct biomarkers and interferon (IFN) signature patterns. A high IFN signature in the B cell active, low symptoms (BALS) cluster predicts disease progression and lymphoma risk.

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Area of Science:

  • Immunology
  • Rheumatology
  • Genetics

Background:

  • Sjögren's disease (SjD) exhibits diverse clinical presentations.
  • Recent cluster analysis identified three phenotypes: B cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms (LSAHS).
  • Understanding distinct SjD phenotypes is crucial for targeted therapies.

Purpose of the Study:

  • To investigate distinct biomarkers associated with SjD patient clusters.
  • To evaluate the prognostic value of the interferon (IFN) signature in these clusters.
  • To correlate IFN signature with disease evolution and treatment outcomes.

Main Methods:

  • Analysis of a 20-year prospective Sjögren's Syndrome cohort (n=395).
  • Comparison of biomarkers including IFN-α2, IFN-γ, CXCL10, CXCL13, BAFF, IL-7, and TNF-RII.
  • Assessment of IFN signature via transcriptomic analysis and correlation with clinical outcomes.

Main Results:

  • Distinct biomarker profiles were observed across BALS, HSA, and LSAHS clusters.
  • A high IFN signature, primarily driven by type I IFN (IFN-α2), was prevalent in the BALS cluster.
  • High IFN signature in BALS patients correlated with increased immunosuppressant use (HR 9.38) and was present in all lymphoma cases.

Conclusions:

  • The three SjD clusters demonstrate unique pathophysiologic mechanisms reflected in IFN signature and immune cell activation markers.
  • A high IFN signature serves as a potential predictor of systemic evolution in the BALS SjD cluster.
  • These findings highlight the importance of IFN pathways in SjD pathogenesis and prognosis.