IVIg attenuates TLR-9 activation in B cells from SLE patients

Introduction: Toll-like receptor-9 (TLR-9) plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to evaluate the influence of intravenous immunoglobulin (IVIg) on CpG oligodeoxynucleotides (ODN-CpG) activated B cells from SLE patients. Methods: Peripheral blood B cells were isolated from 16 SLE patients and 21 healthy age-matched controls. B cells were cultured with ODN-CpG 1μM alone or IVIg (10mg/ml) together with ODN-CpG. After 24-h incubation, B cells and supernatants were collected and analyzed for interleukin (IL)-10, IL-6 secretion, and TLR-9 expression. Results: IVIg decreased the secretion of IL-10 from ODN-CpG-activated B cells isolated from both SLE patients and healthy controls (194±46.2 to 103.2±27.13 pg/ml, p<0.016, 153.2±19 vs 84.6±7.5, p<0.0001, respectively). Similarly, IVIg decreased the secretion of IL-6 from ODN-CpG-activated B cell isolated from both SLE patients and healthy controls (431.2±83 to 307.6±94.3 pg/ml, p<0.0008, 319.5±31 vs 193.3±22.8, p<0.0001, respectively). The decrement of IL-10 and IL-6 secretion was associated with a significant decrease in TLR-9 expression in memory B cells from SLE patients and healthy controls (11.47±1.2 vs 13.29±1.2, p=0.005, 11±0.8 vs 12.8±0.98, p=0.0016, respectively). Conclusions: IVIg attenuates the activation of TLR-9 in B cells from SLE patients, suggesting a novel additional mechanism of IVIg mode of action in these patients.