Patricia López1, Dagmar Scheel-Toellner2, Javier Rodríguez-Carrio2, Luis Caminal-Montero2, Caroline Gordon2, Ana Suárez2. 1. 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. 2. 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.
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. CONCLUSION: 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.
OBJECTIVE: The aim of this study was to investigate the cellular populations and regulatory factors responsible for B-lymphocyte stimulator (BLyS) overexpression in SLEpatients. 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 SLEpatients 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 SLEpatients 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. CONCLUSION: 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 SLEpatients.
Authors: Melissa E Munroe; Rufei Lu; Yan D Zhao; Dustin A Fife; Julie M Robertson; Joel M Guthridge; Timothy B Niewold; George C Tsokos; Michael P Keith; John B Harley; Judith A James Journal: Ann Rheum Dis Date: 2016-01-25 Impact factor: 19.103
Authors: Rufei Lu; Melissa E Munroe; Joel M Guthridge; Krista M Bean; Dustin A Fife; Hua Chen; Samantha R Slight-Webb; Michael P Keith; John B Harley; Judith A James Journal: J Autoimmun Date: 2016-06-20 Impact factor: 7.094
Authors: Judith A James; Joel M Guthridge; Hua Chen; Rufei Lu; Rebecka L Bourn; Krista Bean; Melissa E Munroe; Miles Smith; Eliza Chakravarty; Alan N Baer; Ghaith Noaiseh; Ann Parke; Karen Boyle; Lynette Keyes-Elstein; Andreea Coca; Tammy Utset; Mark C Genovese; Virginia Pascual; Paul J Utz; V Michael Holers; Kevin D Deane; Kathy L Sivils; Teresa Aberle; Daniel J Wallace; James McNamara; Nathalie Franchimont; E William St Clair Journal: Rheumatology (Oxford) Date: 2020-04-01 Impact factor: 7.580