Publication

Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro

Lepse, N., Land, J., Rutgers, A., Kallenberg, C. G. M., Stegeman, C. A., Abdulahad, W. H. & Heeringa, P., Jan-2016, In : Rheumatology. 55, 1, p. 162-172 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Lepse, N., Land, J., Rutgers, A., Kallenberg, C. G. M., Stegeman, C. A., Abdulahad, W. H., & Heeringa, P. (2016). Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro. Rheumatology, 55(1), 162-172. https://doi.org/10.1093/rheumatology/kev293

Author

Lepse, Nikola ; Land, Judith ; Rutgers, Abraham ; Kallenberg, Cees G. M. ; Stegeman, Coen A. ; Abdulahad, Wayel H. ; Heeringa, Peter. / Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro. In: Rheumatology. 2016 ; Vol. 55, No. 1. pp. 162-172.

Harvard

Lepse, N, Land, J, Rutgers, A, Kallenberg, CGM, Stegeman, CA, Abdulahad, WH & Heeringa, P 2016, 'Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro', Rheumatology, vol. 55, no. 1, pp. 162-172. https://doi.org/10.1093/rheumatology/kev293

Standard

Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro. / Lepse, Nikola; Land, Judith; Rutgers, Abraham; Kallenberg, Cees G. M.; Stegeman, Coen A.; Abdulahad, Wayel H.; Heeringa, Peter.

In: Rheumatology, Vol. 55, No. 1, 01.2016, p. 162-172.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Lepse N, Land J, Rutgers A, Kallenberg CGM, Stegeman CA, Abdulahad WH et al. Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro. Rheumatology. 2016 Jan;55(1):162-172. https://doi.org/10.1093/rheumatology/kev293


BibTeX

@article{8380d7f9d58b4908bdb567c58ab0eb27,
title = "Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro",
abstract = "Objectives. Granulomatosis with polyangiitis (GPA) is a relapsing small-vessel vasculitis characterized by circulating ANCA against PR3. The mechanisms that trigger PR3-ANCA production are unknown. The aim of this study was to determine whether endogenous factors [B cell activating factor (BAFF) and IL-21] and exogenous factors [oligodeoxynucleotides containing CpG motifs (CpG-ODN)] synergize in stimulating PR3-ANCA production in GPA patients.Methods. Peripheral blood mononuclear cells from GPA patients and healthy controls (HCs) were cultured in the presence of BAFF and IL-21, with or without CpG-ODN, for 12 days. PR3-ANCA production in culture supernatants was quantified by Phadia EliA. Phenotypic characterization and the influence of CpG-ODN treatment on IL-21 receptor (IL-21R), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) and BAFF receptor (BAFF-R) expression on B cells was analysed by flow cytometry.Results. Stimulation with BAFF and IL-21 significantly increased ANCA production in patient samples, which could be augmented further by addition of CpG-ODN. Stimulation with CpG-ODN increased the percentage of IL-21R(+) and TACI(+) B cells but did not affect BAFF-R expression. GPA patients had an increased percentage of circulating IL-21R(+) and a decreased percentage of TACI(+) circulating memory B cells when compared with HCs. Additionally, patients had decreased expression of BAFF-R on B cells, which was inversely correlated with BAFF concentrations in plasma.Conclusion. Our data demonstrate that endogenous and exogenous factors can synergize to promote PR3-ANCA production. Mechanistically, CpG-ODN up-regulated IL-21R and TACI expression on B cells, possibly sensitizing these cells for IL-21-and BAFF-mediated signals. Agents inhibiting Toll-like receptor 9, BAFF and IL-21 signalling pathways may serve as potential therapeutics for intervention in GPA patients.",
keywords = "GPA, vasculitis, ANCA, B cells, IL-21, BAFF, TLR9, IL-21R, BAFF-R, TACI, ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY, SYSTEMIC-LUPUS-ERYTHEMATOSUS, ANCA-ASSOCIATED VASCULITIS, PRIMARY SJOGRENS-SYNDROME, WEGENERS-GRANULOMATOSIS, DISEASE-ACTIVITY, STAPHYLOCOCCUS-AUREUS, CONSENSUS CONFERENCE, SERUM-LEVELS, T-CELLS",
author = "Nikola Lepse and Judith Land and Abraham Rutgers and Kallenberg, {Cees G. M.} and Stegeman, {Coen A.} and Abdulahad, {Wayel H.} and Peter Heeringa",
note = "{\circledC} The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2016",
month = "1",
doi = "10.1093/rheumatology/kev293",
language = "English",
volume = "55",
pages = "162--172",
journal = "Rheumatology",
issn = "1462-0324",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro

AU - Lepse, Nikola

AU - Land, Judith

AU - Rutgers, Abraham

AU - Kallenberg, Cees G. M.

AU - Stegeman, Coen A.

AU - Abdulahad, Wayel H.

AU - Heeringa, Peter

N1 - © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2016/1

Y1 - 2016/1

N2 - Objectives. Granulomatosis with polyangiitis (GPA) is a relapsing small-vessel vasculitis characterized by circulating ANCA against PR3. The mechanisms that trigger PR3-ANCA production are unknown. The aim of this study was to determine whether endogenous factors [B cell activating factor (BAFF) and IL-21] and exogenous factors [oligodeoxynucleotides containing CpG motifs (CpG-ODN)] synergize in stimulating PR3-ANCA production in GPA patients.Methods. Peripheral blood mononuclear cells from GPA patients and healthy controls (HCs) were cultured in the presence of BAFF and IL-21, with or without CpG-ODN, for 12 days. PR3-ANCA production in culture supernatants was quantified by Phadia EliA. Phenotypic characterization and the influence of CpG-ODN treatment on IL-21 receptor (IL-21R), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) and BAFF receptor (BAFF-R) expression on B cells was analysed by flow cytometry.Results. Stimulation with BAFF and IL-21 significantly increased ANCA production in patient samples, which could be augmented further by addition of CpG-ODN. Stimulation with CpG-ODN increased the percentage of IL-21R(+) and TACI(+) B cells but did not affect BAFF-R expression. GPA patients had an increased percentage of circulating IL-21R(+) and a decreased percentage of TACI(+) circulating memory B cells when compared with HCs. Additionally, patients had decreased expression of BAFF-R on B cells, which was inversely correlated with BAFF concentrations in plasma.Conclusion. Our data demonstrate that endogenous and exogenous factors can synergize to promote PR3-ANCA production. Mechanistically, CpG-ODN up-regulated IL-21R and TACI expression on B cells, possibly sensitizing these cells for IL-21-and BAFF-mediated signals. Agents inhibiting Toll-like receptor 9, BAFF and IL-21 signalling pathways may serve as potential therapeutics for intervention in GPA patients.

AB - Objectives. Granulomatosis with polyangiitis (GPA) is a relapsing small-vessel vasculitis characterized by circulating ANCA against PR3. The mechanisms that trigger PR3-ANCA production are unknown. The aim of this study was to determine whether endogenous factors [B cell activating factor (BAFF) and IL-21] and exogenous factors [oligodeoxynucleotides containing CpG motifs (CpG-ODN)] synergize in stimulating PR3-ANCA production in GPA patients.Methods. Peripheral blood mononuclear cells from GPA patients and healthy controls (HCs) were cultured in the presence of BAFF and IL-21, with or without CpG-ODN, for 12 days. PR3-ANCA production in culture supernatants was quantified by Phadia EliA. Phenotypic characterization and the influence of CpG-ODN treatment on IL-21 receptor (IL-21R), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) and BAFF receptor (BAFF-R) expression on B cells was analysed by flow cytometry.Results. Stimulation with BAFF and IL-21 significantly increased ANCA production in patient samples, which could be augmented further by addition of CpG-ODN. Stimulation with CpG-ODN increased the percentage of IL-21R(+) and TACI(+) B cells but did not affect BAFF-R expression. GPA patients had an increased percentage of circulating IL-21R(+) and a decreased percentage of TACI(+) circulating memory B cells when compared with HCs. Additionally, patients had decreased expression of BAFF-R on B cells, which was inversely correlated with BAFF concentrations in plasma.Conclusion. Our data demonstrate that endogenous and exogenous factors can synergize to promote PR3-ANCA production. Mechanistically, CpG-ODN up-regulated IL-21R and TACI expression on B cells, possibly sensitizing these cells for IL-21-and BAFF-mediated signals. Agents inhibiting Toll-like receptor 9, BAFF and IL-21 signalling pathways may serve as potential therapeutics for intervention in GPA patients.

KW - GPA

KW - vasculitis

KW - ANCA

KW - B cells

KW - IL-21

KW - BAFF

KW - TLR9

KW - IL-21R

KW - BAFF-R

KW - TACI

KW - ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY

KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS

KW - ANCA-ASSOCIATED VASCULITIS

KW - PRIMARY SJOGRENS-SYNDROME

KW - WEGENERS-GRANULOMATOSIS

KW - DISEASE-ACTIVITY

KW - STAPHYLOCOCCUS-AUREUS

KW - CONSENSUS CONFERENCE

KW - SERUM-LEVELS

KW - T-CELLS

U2 - 10.1093/rheumatology/kev293

DO - 10.1093/rheumatology/kev293

M3 - Article

C2 - 26320128

VL - 55

SP - 162

EP - 172

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 1

ER -

ID: 23474346