Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren’s disease - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue RMD Open Année : 2024

Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren’s disease

Renaud Felten
Anne-Perrine Foray
  • Fonction : Auteur
Pascal Schneider
  • Fonction : Auteur
Cindy Marquet
  • Fonction : Auteur
Coralie Pecquet
  • Fonction : Auteur
Jean Sibilia
  • Fonction : Auteur
Fabrice Valette
  • Fonction : Auteur
Lucienne Chatenoud
  • Fonction : Auteur
Jacques-Eric Gottenberg

Résumé

Introduction The therapeutic interest of targeting B-cell activating factor (BAFF) in Sjögren’s disease (SjD) can be suspected from the results of two phase II clinical trials but has not been evaluated in an animal model of the disease. We aimed to evaluate the therapeutic efficacy of this strategy on dryness and salivary gland (SG) infiltrates in the NOD mouse model of SjD. Material and methods Female NOD mice between ages 10 and 18 weeks were treated with a BAFF-blocking monoclonal antibody, Sandy-2 or an isotype control. Dryness was measured by the stimulated salivary flow. Salivary lymphocytic infiltrates were assessed by immunohistochemistry. Blood, SGs, spleen and lymph-node lymphocyte subpopulations were analysed by flow cytometry. SG mRNA expression was analysed by transcriptomic analysis. Results BAFF inhibition significantly decreased SG lymphocytic infiltrates, which was inversely correlated with salivary flow. The treatment markedly decreased B-cell number in SGs, blood, lymph nodes and spleen and increased Foxp3 + regulatory and CD3 + CD4 − CD8 − double negative T-cell numbers in SGs. Conclusion A monoclonal antibody blocking BAFF and depleting B cells had therapeutic effectiveness in the NOD mouse model of SjD. The increase in regulatory T-lymphocyte populations might underlie the efficacy of this treatment.

Dates et versions

hal-04690169 , version 1 (06-09-2024)

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Citer

Renaud Felten, Anne-Perrine Foray, Pascal Schneider, Cindy Marquet, Coralie Pecquet, et al.. Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren’s disease. RMD Open, 2024, 10 (3), pp.e004112. ⟨10.1136/rmdopen-2024-004112⟩. ⟨hal-04690169⟩

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