@misc{10498/36613,
year = {2017},
url = {http://hdl.handle.net/10498/36613},
abstract = {Disturbances 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 (CD19lowCD38high) 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.},
publisher = {Wiley-VCH Verlag},
keywords = {Anti-dsDNA},
keywords = {Anti-ENA},
keywords = {Antibody-secreting cells},
keywords = {Cytokines},
keywords = {Plasma cell niche},
keywords = {SLE},
keywords = {STAT-3},
title = {Clinical relevance of circulating anti-ENA and anti-dsDNA secreting cells from SLE patients and their dependence on STAT-3 activation},
doi = {10.1002/EJI.201646872},
author = {De la Varga MartÍnez, Raquel and Rodríguez Bayona, Beatriz and Añez, Gustavo A. and Medina Varo, Fermín and Pérez Venegas, José Javier and Brieva, José A. and Rodríguez, Carmen},
}