Distinct pathophysiological pathways support stratification of Sjögren's disease based on symptoms, clinical, and routine biological data - Archive ouverte HAL
Article Dans Une Revue Arthritis & rheumatology Année : 2024

Distinct pathophysiological pathways support stratification of Sjögren's disease based on symptoms, clinical, and routine biological data

Yann Nguyen
Jacques‐eric Gottenberg
Aleth Perdriger
  • Fonction : Auteur
Emmanuelle Dernis
  • Fonction : Auteur
Divi Cornec
Valérie Devauchelle-Pensec
Damien Sène
  • Fonction : Auteur
Philippe Dieudé
  • Fonction : Auteur
Marion Couderc
  • Fonction : Auteur
Anne‐laure Fauchais
  • Fonction : Auteur
Claire Larroche
  • Fonction : Auteur
Olivier Vittecoq
  • Fonction : Auteur
Carine Salliot
Eric Hachulla
  • Fonction : Auteur
Véronique Le Guern
  • Fonction : Auteur
Xavier Mariette
  • Fonction : Auteur
Raphaèle Seror
  • Fonction : Auteur
Gaëtane Nocturne

Résumé

Objective Recently, three distinct phenotypes of Sjögren's disease (SjD) patients have been described, based on cluster analysis: B‐cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms (LSAHS). We aimed to assess whether these clusters were associated with distinct biomarkers and the prognostic value of IFN signature. Methods The ASSESS cohort is a 20‐year prospective cohort of SjD patients. The following biomarkers were compared: IFN‐α2, IFN‐γ, CXCL10, CXCL13, BAFF, IL7, FLT3, CCL19, and TNFRII. IFN signature was assessed using transcriptomic analysis. We then compared systemic and symptomatic evolution, and the risk of new immunosuppressant prescription and of lymphoma, according to the IFN signature across the three clusters. Results 395 patients (94% female, median age 53 [43‐63] years) were included. Higher levels of CXCL‐13, IL7, and TNF‐RII levels were found in the BALS and HSA clusters compared to the LSAHS cluster. A high IFN signature was mainly found in the BALS cluster (57%, vs. 48%, and 38% in the HSA and LSAHS clusters, respectively). This IFN signature was mainly driven by type I IFN, with higher levels of IFN‐ α2. In the BALS cluster, a high IFN signature was associated with a higher risk of new immunosuppressant treatment (HR 9.38; 95% CI 1.22‐72.16). All lymphoma occurred in patients with high IFN signature. Conclusion The three SjD clusters displayed distinct expression of IFN signature, and markers of T‐ and B‐cell activation, confirming distinct pathophysiological mechanisms. High IFN signature could predict systemic evolution in the BALS cluster.
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Dates et versions

hal-04855917 , version 1 (26-12-2024)

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Yann Nguyen, Maxime Beydon, Jacques‐eric Gottenberg, Jacques Morel, Aleth Perdriger, et al.. Distinct pathophysiological pathways support stratification of Sjögren's disease based on symptoms, clinical, and routine biological data. Arthritis & rheumatology, 2024, ⟨10.1002/art.43096⟩. ⟨hal-04855917⟩
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