Effects of rituximab and dexamethasone on regulatory and proinflammatory B-cell subsets in patients with primary immune thrombocytopenia

Eur J Haematol. 2018 Jan;100(1):45-52. doi: 10.1111/ejh.12978. Epub 2017 Oct 18.

Abstract

Objective: To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM).

Methods: Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors. Expression of the cell-surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL-6 and IL-10 were measured by flow cytometry.

Results: PBMCs from ITP patients at baseline contained a lower proportion of IL-10+ B cells (P < .01) and IL-6+ B cells (P < .01) than healthy controls. All patients responded to therapy and levels were normalized at 12 months. The proportion of CD5+ B cells increased (P < .01) and CD27+ memory B cells decreased (P < .05) 12 months after treatment with RTX+DXM compared to baseline, with an inverse correlation between platelet numbers and the proportion of CD27+ B cells (R = -0.71; P < .05).

Conclusion: Both treatment regimens normalized the frequencies of cytokine-producing B cells. The additional increase in CD5+ B cells after RTX+DXM is compatible with induction of Bregs.

Keywords: B-cells; cytokines; immune thrombocytopenia; rituximab; surface markers.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • B-Lymphocyte Subsets / drug effects*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes, Regulatory / drug effects*
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism
  • Biomarkers
  • Case-Control Studies
  • Cytokines / metabolism
  • Dexamethasone / pharmacology*
  • Dexamethasone / therapeutic use
  • Female
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Immunophenotyping
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Phenotype
  • Platelet Count
  • Purpura, Thrombocytopenic, Idiopathic / diagnosis
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic / immunology*
  • Rituximab / pharmacology*
  • Rituximab / therapeutic use
  • Young Adult

Substances

  • Autoantibodies
  • Biomarkers
  • Cytokines
  • Immunologic Factors
  • Rituximab
  • Dexamethasone