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

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Abstract

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.

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Authors and Affiliations

  1. Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Haifa, 31048, Israel

    Aharon Kessel, Regina Peri, Tharwat Haj, Ayelet Snir, Edmond Sabo & Elias Toubi

  2. Department of Medicine A, Bnai Zion Medical Center, Technion Faculty of Medicine, Haifa, Israel

    Gleb Slobodin

  3. Rheumatology Department, Bnai Zion Medical Center, Technion Faculty of Medicine, Haifa, Israel

    Itzhak Rosner

  4. Department of Medicine B and the Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Yehuda Shoenfeld

  5. Incumbent of the Laura Schwarz Kipp Chair for Research of Autoimmune Diseases, Sackler faculty of Medicine, Tel Aviv, Israel

    Yehuda Shoenfeld

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  1. Aharon Kessel
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Correspondence to Aharon Kessel.

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Kessel, A., Peri, R., Haj, T. et al. IVIg Attenuates TLR-9 Activation in B Cells from SLE Patients. J Clin Immunol 31, 30–38 (2011). https://doi.org/10.1007/s10875-010-9469-3

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  • DOI: https://doi.org/10.1007/s10875-010-9469-3

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