Publication

Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis

Land, J., Lintermans, L. L., Stegeman, C. A., Munoz-Elias, E. J., Tarcha, E. J., Iadonato, S. P., Heeringa, P., Rutgers, A. & Abdulahad, W. H., 26-Sep-2017, In : Frontiers in Immunology. 8, 9 p., 1205.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Land, J., Lintermans, L. L., Stegeman, C. A., Munoz-Elias, E. J., Tarcha, E. J., Iadonato, S. P., ... Abdulahad, W. H. (2017). Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis. Frontiers in Immunology, 8, [1205]. https://doi.org/10.3389/fimmu.2017.01205

Author

Land, Judith ; Lintermans, Lucas L. ; Stegeman, Coen A. ; Munoz-Elias, Ernesto J. ; Tarcha, Eric J. ; Iadonato, Shawn P. ; Heeringa, Peter ; Rutgers, Abraham ; Abdulahad, Wayel H. / Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis. In: Frontiers in Immunology. 2017 ; Vol. 8.

Harvard

Land, J, Lintermans, LL, Stegeman, CA, Munoz-Elias, EJ, Tarcha, EJ, Iadonato, SP, Heeringa, P, Rutgers, A & Abdulahad, WH 2017, 'Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis' Frontiers in Immunology, vol. 8, 1205. https://doi.org/10.3389/fimmu.2017.01205

Standard

Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis. / Land, Judith; Lintermans, Lucas L.; Stegeman, Coen A.; Munoz-Elias, Ernesto J.; Tarcha, Eric J.; Iadonato, Shawn P.; Heeringa, Peter; Rutgers, Abraham; Abdulahad, Wayel H.

In: Frontiers in Immunology, Vol. 8, 1205, 26.09.2017.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Land J, Lintermans LL, Stegeman CA, Munoz-Elias EJ, Tarcha EJ, Iadonato SP et al. Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis. Frontiers in Immunology. 2017 Sep 26;8. 1205. https://doi.org/10.3389/fimmu.2017.01205


BibTeX

@article{966d8693b7d24004b8292d346812d149,
title = "Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis",
abstract = "B cells are central to the pathogenesis of granulomatosis with polyangiitis (GPA), exhibiting both (auto) antibody-dependent and -independent properties. Class-switched memory B cells in particular are a major source of pathogenic autoantibodies. These cells are characterized by high expression levels of Kv1.3 potassium channels, which may offer therapeutic potential for Kv1.3 blockade. In this study, we investigated the effect of the highly potent Kv1.3 blocker ShK-186 on B cell properties in GPA in vitro. Circulating B cell subsets were determined from 33 GPA patients and 17 healthy controls (HCs). Peripheral blood mononuclear cells (PBMCs) from GPA patients, and HCs were stimulated in vitro in the presence and absence of ShK-186. The production of total and antineutrophil cytoplasmic antibodies targeting proteinase 3 (PR3-ANCA) IgG was analyzed by enzyme-linked immunosorbent assay and Phadia EliA, respectively. In addition, effects of ShK-186 on B cell proliferation and cytokine production were determined by flow cytometry. The frequency of circulating switched and unswitched memory B cells was decreased in GPA patients as compared to HC. ShK-186 suppressed the production of both total and PR3-ANCA IgG in stimulated PBMCs. A strong decrease in production of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-2, and interferon gamma was observed upon ShK-186 treatment, while effects on IL-10 production were less pronounced. As such, ShK-186 modulated the TNF alpha/IL-10 ratio among B cells, resulting in a relative increase in the regulatory B cell pool. ShK-186 modulates the effector functions of B cells in vitro by decreasing autoantibody and pro-inflammatory cytokine production. Kv1.3 channel blockade may hold promise as a novel therapeutic strategy in GPA and other B cell-mediated autoimmune disorders.",
keywords = "granulomatosis and polyangiitis, B cells, Kv1.3 potassium channels, antineutrophil cytoplasmic antibody, cytokines, ANCA-ASSOCIATED VASCULITIS, PRIMARY SJOGRENS-SYNDROME, RHEUMATOID-ARTHRITIS, DEPRESSED PERCENTAGE, INADEQUATE RESPONSE, ION CHANNELS, PHASE-II, MEMORY B, PATHOGENESIS, RITUXIMAB",
author = "Judith Land and Lintermans, {Lucas L.} and Stegeman, {Coen A.} and Munoz-Elias, {Ernesto J.} and Tarcha, {Eric J.} and Iadonato, {Shawn P.} and Peter Heeringa and Abraham Rutgers and Abdulahad, {Wayel H.}",
year = "2017",
month = "9",
day = "26",
doi = "10.3389/fimmu.2017.01205",
language = "English",
volume = "8",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media SA",

}

RIS

TY - JOUR

T1 - Kv1.3 channel Blockade Modulates the effector Function of B cells in granulomatosis with Polyangiitis

AU - Land, Judith

AU - Lintermans, Lucas L.

AU - Stegeman, Coen A.

AU - Munoz-Elias, Ernesto J.

AU - Tarcha, Eric J.

AU - Iadonato, Shawn P.

AU - Heeringa, Peter

AU - Rutgers, Abraham

AU - Abdulahad, Wayel H.

PY - 2017/9/26

Y1 - 2017/9/26

N2 - B cells are central to the pathogenesis of granulomatosis with polyangiitis (GPA), exhibiting both (auto) antibody-dependent and -independent properties. Class-switched memory B cells in particular are a major source of pathogenic autoantibodies. These cells are characterized by high expression levels of Kv1.3 potassium channels, which may offer therapeutic potential for Kv1.3 blockade. In this study, we investigated the effect of the highly potent Kv1.3 blocker ShK-186 on B cell properties in GPA in vitro. Circulating B cell subsets were determined from 33 GPA patients and 17 healthy controls (HCs). Peripheral blood mononuclear cells (PBMCs) from GPA patients, and HCs were stimulated in vitro in the presence and absence of ShK-186. The production of total and antineutrophil cytoplasmic antibodies targeting proteinase 3 (PR3-ANCA) IgG was analyzed by enzyme-linked immunosorbent assay and Phadia EliA, respectively. In addition, effects of ShK-186 on B cell proliferation and cytokine production were determined by flow cytometry. The frequency of circulating switched and unswitched memory B cells was decreased in GPA patients as compared to HC. ShK-186 suppressed the production of both total and PR3-ANCA IgG in stimulated PBMCs. A strong decrease in production of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-2, and interferon gamma was observed upon ShK-186 treatment, while effects on IL-10 production were less pronounced. As such, ShK-186 modulated the TNF alpha/IL-10 ratio among B cells, resulting in a relative increase in the regulatory B cell pool. ShK-186 modulates the effector functions of B cells in vitro by decreasing autoantibody and pro-inflammatory cytokine production. Kv1.3 channel blockade may hold promise as a novel therapeutic strategy in GPA and other B cell-mediated autoimmune disorders.

AB - B cells are central to the pathogenesis of granulomatosis with polyangiitis (GPA), exhibiting both (auto) antibody-dependent and -independent properties. Class-switched memory B cells in particular are a major source of pathogenic autoantibodies. These cells are characterized by high expression levels of Kv1.3 potassium channels, which may offer therapeutic potential for Kv1.3 blockade. In this study, we investigated the effect of the highly potent Kv1.3 blocker ShK-186 on B cell properties in GPA in vitro. Circulating B cell subsets were determined from 33 GPA patients and 17 healthy controls (HCs). Peripheral blood mononuclear cells (PBMCs) from GPA patients, and HCs were stimulated in vitro in the presence and absence of ShK-186. The production of total and antineutrophil cytoplasmic antibodies targeting proteinase 3 (PR3-ANCA) IgG was analyzed by enzyme-linked immunosorbent assay and Phadia EliA, respectively. In addition, effects of ShK-186 on B cell proliferation and cytokine production were determined by flow cytometry. The frequency of circulating switched and unswitched memory B cells was decreased in GPA patients as compared to HC. ShK-186 suppressed the production of both total and PR3-ANCA IgG in stimulated PBMCs. A strong decrease in production of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-2, and interferon gamma was observed upon ShK-186 treatment, while effects on IL-10 production were less pronounced. As such, ShK-186 modulated the TNF alpha/IL-10 ratio among B cells, resulting in a relative increase in the regulatory B cell pool. ShK-186 modulates the effector functions of B cells in vitro by decreasing autoantibody and pro-inflammatory cytokine production. Kv1.3 channel blockade may hold promise as a novel therapeutic strategy in GPA and other B cell-mediated autoimmune disorders.

KW - granulomatosis and polyangiitis

KW - B cells

KW - Kv1.3 potassium channels

KW - antineutrophil cytoplasmic antibody

KW - cytokines

KW - ANCA-ASSOCIATED VASCULITIS

KW - PRIMARY SJOGRENS-SYNDROME

KW - RHEUMATOID-ARTHRITIS

KW - DEPRESSED PERCENTAGE

KW - INADEQUATE RESPONSE

KW - ION CHANNELS

KW - PHASE-II

KW - MEMORY B

KW - PATHOGENESIS

KW - RITUXIMAB

U2 - 10.3389/fimmu.2017.01205

DO - 10.3389/fimmu.2017.01205

M3 - Article

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1205

ER -

ID: 48673687