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

Emily L Williams*, Madeleine L Stimpson, Philippa J P Lait, Lauren P Schewitz-Bowers, Lauren Jones, Ashwin Dhanda, Richard W J Lee, Charlotte A Bradbury

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
27 Downloads (Pure)

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 IL-17A and IFN-γ. The role of monocytes 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 monocytes. Using multiparameter flow cytometry analysis, we demonstrate expansion of intermediate monocytes (CD14++CD16+) in untreated newly diagnosed, ITP patients, with these cells displaying a pro-inflammatory phenotype, characterised by enhanced expression of CD64 and CD80. After 2 weeks of prednisolone treatment (1mg/kg daily), the proportion of intermediate monocytes reduced, with enhanced expression of the anti-inflammatory markers CD206 and CD163. Healthy control monocytes were distinctly different from those from ITP patients before and following 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 monocytes in ITP pathogenesis and clinical response to GC-therapy.
Original languageEnglish
Pages (from-to)375-384
Number of pages10
JournalBritish Journal of Haematology
Volume192
Issue number2
Early online date18 Dec 2020
DOIs
Publication statusPublished - 18 Jan 2021

Bibliographical note

Funding Information:
We thank Andrew Herman and Lorena Sueiro Ballesteros for their flow cytometry support. We also thank the Bristol Eye Hospital Clinical Research Unit for their support in collecting HC peripheral blood samples. This research was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Funding Information:
We thank Andrew Herman and Lorena Sueiro Ballesteros for their flow cytometry support. We also thank the Bristol Eye Hospital Clinical Research Unit for their support in collecting HC peripheral blood samples. This research was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Publisher Copyright:
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons

Keywords

  • autoimmunity
  • glucorticoids
  • steroids
  • immune thrombocytopenia
  • monocyte subsets

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