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Pré-Publication, Document De Travail Année : 2023

Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjogren's disease

Antoine Hamon
  • Fonction : Auteur
Audrey Aussy
  • Fonction : Auteur
Etienne E. Birmelé
Etienne Becht
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Résumé

Primary Sjogren disease (pSD) is an autoimmune disease characterized by lymphoid infiltration of exocrine glands leading to dryness of the mucosal surfaces and by the production of autoantibodies. The pathophysiology of pSD remains elusive and no treatment with demonstrated efficacy is available yet. To better understand the biology underlying pSD heterogeneity, we aimed at identifying Consensus gene Modules (CMs) that summarize the high-dimensional transcriptomic data of whole blood samples in pSD patients. We performed unsupervised gene classification on four data sets and identified thirteen CMs. We annotated and interpreted each of these CMs as corresponding to cell type abundances or biological functions by using gene set enrichment analyses and transcriptomic profiles of sorted blood cell subsets. Correlation with independently measured cell type abundances by flow cytometry confirmed these annotations. We used these CMs to reconcile previously proposed patient stratifications of pSD. Importantly, we showed that the expression of modules representing lymphocytes and erythrocytes before treatment initiation is associated with response to hydroxychloroquine and leflunomide combination therapy in a clinical trial. These consensus modules will help the identification and translation of blood-based predictive biomarkers for the treatment of pSD.

Dates et versions

pasteur-04250559 , version 1 (19-10-2023)

Identifiants

Citer

Cheima Boudjeniba, Perrine Soret, Diana Trutschel, Antoine Hamon, Valentin Baloche, et al.. Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjogren's disease. 2023. ⟨pasteur-04250559⟩
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