RT Journal Article
SR Electronic
T1 Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren’s disease
JF RMD Open
JO RMD Open
FD EULAR
SP e004112
DO 10.1136/rmdopen-2024-004112
VO 10
IS 3
A1 Felten, Renaud
A1 Foray, Anne-Perrine
A1 Schneider, Pascal
A1 Marquet, Cindy
A1 Pecquet, Coralie
A1 Monneaux, Fanny
A1 Dumortier, Hélène
A1 Sibilia, Jean
A1 Valette, Fabrice
A1 Chatenoud, Lucienne
A1 Gottenberg, Jacques-Eric
YR 2024
UL http://rmdopen.bmj.com/content/10/3/e004112.abstract
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.