Interferon-α-induced B-lymphocyte stimulator expression and mobilization in healthy and systemic lupus erthymatosus monocytes

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-alpha, IFN-alpha, IFN-gamma, 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-alpha and SLE-ICs induced a progressive increase in surface-bound BLyS with respect to the intracellular stores. IFN-alpha-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-alpha 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.