IVIg Attenuates TLR-9 Activation in B Cells from SLE Patients

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. Peripheral blood B cells were isolated from 16 SLE patients and 21 healthy age-matched controls. B cells were cultured with ODN-CpG 1 mu M 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. 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). 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.