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Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern

BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is performed in patients with aggressive forms of systemic sclerosis (SSc). The profile of B cell reconstitution after aHSCT is not fully understood. The aim of this study was to investigate changes of B cell subsets and cytokine...

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Autores principales: Gernert, Michael, Tony, Hans-Peter, Schwaneck, Eva Christina, Gadeholt, Ottar, Schmalzing, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489316/
https://www.ncbi.nlm.nih.gov/pubmed/31036055
http://dx.doi.org/10.1186/s13075-019-1889-8
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author Gernert, Michael
Tony, Hans-Peter
Schwaneck, Eva Christina
Gadeholt, Ottar
Schmalzing, Marc
author_facet Gernert, Michael
Tony, Hans-Peter
Schwaneck, Eva Christina
Gadeholt, Ottar
Schmalzing, Marc
author_sort Gernert, Michael
collection PubMed
description BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is performed in patients with aggressive forms of systemic sclerosis (SSc). The profile of B cell reconstitution after aHSCT is not fully understood. The aim of this study was to investigate changes of B cell subsets and cytokine production of B cells in patients with SSc after aHSCT. METHODS: Peripheral blood of six patients with SSc was collected at defined intervals up to 16 months after aHSCT. Immunophenotyping was performed, and B cell function was determined by measuring cytokine secretion in supernatants of stimulated B cell cultures. RESULTS: Within 1 month after aHSCT, a peak in the percentage of CD38(++)/CD10(+)/IgD(+) transitional B cells and CD38(++)/CD27(++)/IgD(−) plasmablasts was detected. Long-term changes persisted up to 14 months after aHSCT and showed an increased percentage of total B cells; the absolute B cell number did not change significantly. Within the B cell compartment, an increased CD27/IgD(+) naïve B cell percentage was found whereas decreased percentages of CD27(+)/IgD(+) pre-switched memory, CD27(+)/IgD(−) post-switched memory, and CD27(−)/IgD(−) double-negative B cells were seen after aHSCT. Cytokine secretion in B cell cultures showed significantly increased IL-10 concentrations 13 to 16 months after aHSCT. CONCLUSION: A changed composition of the B cell compartment is present for up to 14 months after aHSCT indicating positive persisting effects of aHSCT on B cell homeostasis. The cytokine secretion profile of B cells changes in the long term and shows an increased production of the immune regulatory cytokine IL-10 after aHSCT. These findings might promote the clinical improvements after aHSCT in SSc patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1889-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-64893162019-06-04 Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern Gernert, Michael Tony, Hans-Peter Schwaneck, Eva Christina Gadeholt, Ottar Schmalzing, Marc Arthritis Res Ther Research Article BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is performed in patients with aggressive forms of systemic sclerosis (SSc). The profile of B cell reconstitution after aHSCT is not fully understood. The aim of this study was to investigate changes of B cell subsets and cytokine production of B cells in patients with SSc after aHSCT. METHODS: Peripheral blood of six patients with SSc was collected at defined intervals up to 16 months after aHSCT. Immunophenotyping was performed, and B cell function was determined by measuring cytokine secretion in supernatants of stimulated B cell cultures. RESULTS: Within 1 month after aHSCT, a peak in the percentage of CD38(++)/CD10(+)/IgD(+) transitional B cells and CD38(++)/CD27(++)/IgD(−) plasmablasts was detected. Long-term changes persisted up to 14 months after aHSCT and showed an increased percentage of total B cells; the absolute B cell number did not change significantly. Within the B cell compartment, an increased CD27/IgD(+) naïve B cell percentage was found whereas decreased percentages of CD27(+)/IgD(+) pre-switched memory, CD27(+)/IgD(−) post-switched memory, and CD27(−)/IgD(−) double-negative B cells were seen after aHSCT. Cytokine secretion in B cell cultures showed significantly increased IL-10 concentrations 13 to 16 months after aHSCT. CONCLUSION: A changed composition of the B cell compartment is present for up to 14 months after aHSCT indicating positive persisting effects of aHSCT on B cell homeostasis. The cytokine secretion profile of B cells changes in the long term and shows an increased production of the immune regulatory cytokine IL-10 after aHSCT. These findings might promote the clinical improvements after aHSCT in SSc patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1889-8) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-29 2019 /pmc/articles/PMC6489316/ /pubmed/31036055 http://dx.doi.org/10.1186/s13075-019-1889-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gernert, Michael
Tony, Hans-Peter
Schwaneck, Eva Christina
Gadeholt, Ottar
Schmalzing, Marc
Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern
title Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern
title_full Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern
title_fullStr Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern
title_full_unstemmed Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern
title_short Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern
title_sort autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in b cell homeostasis toward an anti-inflammatory b cell cytokine pattern
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489316/
https://www.ncbi.nlm.nih.gov/pubmed/31036055
http://dx.doi.org/10.1186/s13075-019-1889-8
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