High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcgamma receptors on monocytes in patients with primary immune thrombocytopenia

Blood. 2011 Feb 10;117(6):2061-9. doi: 10.1182/blood-2010-07-295477. Epub 2010 Dec 3.

Abstract

The human Fcγ receptor (FcγR) system is composed of 2 opposing families, the activating FcγRs (FcγRI, FcγRIIa, and FcγRIII) and the inhibitory FcγR (FcγRIIb). The disturbed balance of the activating and inhibitory FcγRs has been implicated in the pathogenesis of many autoimmune diseases. In this study, the expression of FcγRs on monocytes was determined in 23 patients with primary immune thrombocytopenia (ITP) before and after high-dose dexamethasone (HD-DXM) treatment. The FcγRI expression was significantly higher in ITP patients and decreased after HD-DXM treatment. The ratio of FcγRIIa/IIb mRNA expression on monocytes was significantly higher in untreated patients than in healthy controls. After HD-DXM therapy, the ratio decreased and the increased expression of FcγRIIb mRNA and protein coincided with a remarkable decrease in the expression of FcγRIIa, FcγRI, and monocyte phagocytic capacity. There was no significant difference in FcγRIII expression on monocytes between patients and controls. In vitro cell-culture experiments showed that DXM could induce FcγRIIa and FcγRIIb expression in monocytes from ITP patients, with FcγRIIb at higher amplitudes. These findings suggested that the disturbed FcγR balance might play a role in the pathogenesis of ITP, and that HD-DXM therapy could shift monocyte FcγR balance toward the inhibitory FcγRIIb in patients with ITP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • DNA Primers / genetics
  • Dexamethasone / administration & dosage*
  • Female
  • Gene Expression / drug effects
  • Glucocorticoids / administration & dosage
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / immunology*
  • Phagocytosis / drug effects
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy*
  • Purpura, Thrombocytopenic, Idiopathic / genetics
  • Purpura, Thrombocytopenic, Idiopathic / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, IgG / genetics*
  • Receptors, IgG / metabolism*
  • Young Adult

Substances

  • DNA Primers
  • FCGR1A protein, human
  • FCGR2A protein, human
  • FCGR2B protein, human
  • Glucocorticoids
  • IL4 protein, human
  • RNA, Messenger
  • Receptors, IgG
  • Interleukin-4
  • Dexamethasone
  • Interferon-gamma