PT - JOURNAL ARTICLE AU - Felten, Renaud AU - Foray, Anne-Perrine AU - Schneider, Pascal AU - Marquet, Cindy AU - Pecquet, Coralie AU - Monneaux, Fanny AU - Dumortier, Hélène AU - Sibilia, Jean AU - Valette, Fabrice AU - Chatenoud, Lucienne AU - Gottenberg, Jacques-Eric TI - Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren’s disease AID - 10.1136/rmdopen-2024-004112 DP - 2024 Aug 01 TA - RMD Open PG - e004112 VI - 10 IP - 3 4099 - http://rmdopen.bmj.com/content/10/3/e004112.short 4100 - http://rmdopen.bmj.com/content/10/3/e004112.full SO - RMD Open2024 Aug 01; 10 AB - 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.Data are available upon reasonable request. The data underlying this article will be shared on reasonable request to the corresponding author. Datasets are available on request: the raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.