Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14 ++ CD16 + intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype

Br J Haematol. 2021 Jan;192(2):375-384. doi: 10.1111/bjh.17205. Epub 2020 Dec 18.

Abstract

Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4+ T-helper subset distribution and enhanced production of pro-inflammatory cytokines such as interleukin 17A and interferon gamma. The role of monocytes (MCs) in ITP is less widely described, but innate immune cells have a role in shaping CD4+ T-cell phenotypes. Glucocorticoids (GCs) are commonly used for first-line ITP treatment and modulate a broad range of immune cells including T cells and MCs. Using multiparameter flow cytometry analysis, we demonstrate the expansion of intermediate MCs (CD14++ CD16+ ) in untreated patients with newly diagnosed ITP, with these cells displaying a pro-inflammatory phenotype, characterised by enhanced expression of CD64 and CD80. After 2 weeks of prednisolone treatment (1 mg/kg daily), the proportion of intermediate MCs reduced, with enhanced expression of the anti-inflammatory markers CD206 and CD163. Healthy control MCs were distinctly different than MCs from patients with ITP before and after GC treatment. Furthermore, the GC-induced phenotype was not observed in patients with chronic ITP receiving thrombopoietin receptor agonists. These data suggest a role of MCs in ITP pathogenesis and clinical response to GC therapy.

Keywords: autoimmunity; glucocorticoids; immune thrombocytopenia; monocyte subsets; steroids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cells, Cultured
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / pathology
  • Lipopolysaccharide Receptors / analysis*
  • Lipopolysaccharide Receptors / immunology
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / pathology
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy*
  • Purpura, Thrombocytopenic, Idiopathic / immunology
  • Receptors, IgG / analysis*
  • Receptors, IgG / immunology
  • Young Adult

Substances

  • Glucocorticoids
  • Lipopolysaccharide Receptors
  • Receptors, IgG