de la Varga Martínez, RaquelRodríguez-Bayona, BeatrizAñez, Gustavo AMedina Varo, FermínPérez Venegas, José JBrieva, José ARodríguez, Carmen2023-01-252023-01-252017-05-23http://hdl.handle.net/10668/11156Disturbances of plasma cell homeostasis and auto-antibody production are hallmarks of systemic lupus erythematosus. The aim of this study was to explore the presence of circulating anti-ENA and anti-dsDNA antibody-secreting cells, to determine their dependence on plasma cell-niche cytokines and to analyze their clinical value. The study was performed in SLE patients with serum anti-ENA and/or anti-dsDNA antibodies (n = 57). Enriched B-cell fractions and sorted antibody-secreting cells (CD19low CD38high ) were obtained from blood. dsDNA- and ENA-specific antibody-secreting cells were identified as cells capable of active auto-antibody production in culture. The addition of a combination of IL-6, IL-21, BAFF, APRIL, and CXCL12 to the cultures significantly augmented auto-antibody production and antibody-secreting cell proliferation, whereas it diminished apoptosis. The effect on auto-antibody production was dependent on STAT-3 activation as it was abrogated in the presence of the JAK/STAT-3 pathway inhibitors ruxolitinib and stattic. Among patients with serum anti-dsDNA antibodies, the detection of circulating anti-dsDNA-antibody-secreting cells was associated with higher disease activity markers. In conclusion, auto-antibody production in response to plasma cell-niche cytokines that are usually at high levels in SLE patients is dependent on JAK/STAT-3 activation. Thus, patients with circulating anti-dsDNA antibody-secreting cells and active disease could potentially benefit from therapies targeting the JAK/STAT3 pathway.enAnti-ENAAnti-dsDNAAntibody-secreting cellsCytokinesPlasma cell nicheSLESTAT-3AdolescentAdultAgedAntibodies, AntinuclearAntibody-Producing CellsApoptosisB-Cell Activating FactorCell ProliferationChemokine CXCL2Cyclic S-OxidesDNAFemaleHumansInterleukin-6InterleukinsLupus Erythematosus, SystemicMaleMiddle AgedNitrilesPyrazolesPyrimidinesSTAT3 Transcription FactorTumor Necrosis Factor Ligand Superfamily Member 13Young Adultresearch article28463395open access10.1002/eji.2016468721521-4141https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eji.201646872