title: Interferon-α-induced B-lymphocyte stimulator expression and mobilization in healthy and systemic lupus erthymatosus monocytes.
abstract: OBJECTIVE
  The aim of this study was to investigate the cellular populations and regulatory factors responsible for B-lymphocyte stimulator (BLyS) overexpression in SLE patients.
  
  
  METHODS
  Surface and intracellular BLyS levels were quantified by flow cytometry in healthy and SLE monocytes cultured in the presence of TNF-α, IFN-α, IFN-γ, GM-CSF and SLE immune complexes (SLE-ICs), while soluble BLyS was measured by ELISA. Also, both surface and intracellular BLyS expression by different cell subsets was determined in 23 SLE patients and 16 healthy controls. Disease activity was assessed using classic BILAG index.
  
  
  RESULTS
  In vitro experiments using healthy monocytes showed that IFN-α and SLE-ICs induced a progressive increase in surface-bound BLyS with respect to the intracellular stores. IFN-α-treated SLE monocytes, especially from patients with high anti-dsDNA levels or disease activity, exhibited higher intracellular levels of BLyS that was mobilized to the membrane more rapidly and subsequently released. Furthermore, ex vivo analysis of SLE patients revealed up-regulated BLyS expression in B cells, myeloid and plasmacytoid dendritic cells (DCs), whereas active patients had an increased surface:intracellular BLyS ratio in monocytes and myeloid DCs.
  
  
  CONCLUSIONS
  Monocyte BLyS induction and mobilization from intra- to extracellular compartments seems to be influenced by IFN-α and disease activity or anti-dsDNA levels. Accordingly, monocytes and myeloid DCs from active patients presented the highest membrane-bound:intracellular BLyS ratio. In addition, expression levels in several blood cells support the existence of generalized immune stimulation in SLE patients.
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain. lopezpatricia@uniovi.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Scheel-Toellner
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Carrio
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Caminal-Montero
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gordon
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology; D053264:B-Cell Activating Factor / Q000096:biosynthesis / Q000097:blood*; D016022:Case-Control Studies; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D000936:Antigen-Antibody Complex; D053264:B-Cell Activating Factor; D016207:Cytokines; D016898:Interferon-alpha
keywords: BAFF; BLyS; IFN-α; myeloid cells; systemic lupus erythematosus