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

Arthritis Res Ther. 2019 Apr 29;21(1):106. doi: 10.1186/s13075-019-1889-8.

Abstract

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.

Keywords: Autologous hematopoietic stem cell transplantation; B cells; Interleukin-10; Memory B cells; Systemic sclerosis; naïve B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cytokines / blood
  • Cytokines / immunology*
  • Female
  • Hematopoietic Stem Cell Transplantation / trends*
  • Homeostasis / physiology*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / therapy*
  • Transplantation, Autologous / trends
  • Young Adult

Substances

  • Cytokines