Expansion of toll‐like receptor 9–expressing B cells in active systemic lupus erythematosus: Implications for the induction and maintenance of the autoimmune process

Abstract

Objective. Toll-like receptors (TLRs) are patternassociated receptors in innate immunity that may be involved in the recognition of self antigens and the production of pathogenic autoantibodies. This study was undertaken to examine the expression and function of various TLRs in subpopulations of peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods. The expression of TLRs in PBMCs from 50 SLE patients with active disease (SLE Disease Activity Index [SLEDAI] score >8; n ‫؍‬ 26) or inactive disease (SLEDAI score <8; n ‫؍‬ 24) and 20 healthy controls was studied by flow cytometry. TLR expression was assessed on various subpopulations of PBMCs (TLR-2 and TLR-4 by membrane staining; TLR-3 and TLR-9 by intracellular staining). TLR function was accessed by stimulating PBMCs with specific ligands.Results. The proportion of B cells and monocytes expressing TLR-9 was higher among patients with active SLE (mean ؎ SD 49.5 ؎ 24.4% and 30.7 ؎ 24.1%, respectively) than among patients with inactive disease Conclusion. In patients with active SLE, the proportion of peripheral blood memory B cells and plasma cells expressing TLR-9 is increased. Endogenous nucleic acids released during apoptotic cell death may stimulate B cells via TLR-9 and contribute to SLE pathogenesis.

Innate immune response gene expression profiles characterize primary antiphospholipid syndrome

“…A similar mechanism involving plasmacytoid dendritic cells has been suggested for SLE and Sjogren's syndrome, although such a mechanism seems to be associated to TLR9 activation by dsDNA molecules exposed on the plasma membrane of apoptotic cells. 17,27 The upregulated expression of phospholipids scramblase (PLSCR1), a member of a family of membrane proteins that contributes to the reorganization of plasma membrane phospholipids occurring upon cell injury or apoptosis 28 or the upregulation of LGALS and CD14, two receptors involved in the clearance of apoptotic cells, provides a link between our observations in PAPS with dysregulation of apoptosis and/or handling of apoptotic cells.…”

Focus on systemic lupus erythematosus in Indigenous Australians: towards a better understanding of autoimmune diseases

“…Although desirable as part of an anti-microbial response, SLE, as well as primary Sjögren syndrome, are characterised by up-regulated expression of type I IFN and an 'IFN signature', 60,61 suggesting overexpression of genes induced by the type I IFNa. 62 Furthermore, increased expression of TLR-7 and -9 and IFNa in peripheral blood mononuclear cells 63 and increased TLR-9 positive B cells in the blood 64 have been reported in SLE patients. Finally, effective treatment of SLE by anti-malarial drugs is reportedly through inhibition of endosomal TLR-mediated signalling, such as TLR-7 and TLR-9.…”

Toll-like receptor signal transduction

“…In patients with active SLE (systemic lupus erythematosus), the proportion of peripheral blood memory B cells and plasma cells expressing TLR9 is increased. Endogenous nucleic acids released during apoptotic cell death may stimulate B cells via TLR9 and contribute to SLE pathogenesis (Papadimitraki et al, 2006).…”