Foxp3 methylation status in children with primary immune thrombocytopenia

Hum Immunol. 2014 Nov;75(11):1115-9. doi: 10.1016/j.humimm.2014.09.018. Epub 2014 Oct 7.

Abstract

Aim: To investigate the status of DNA methylation in the Foxp3 promoter in pediatric ITP patients and assess the role of DNA methylation of Treg cells in the pathogenesis of ITP.

Methods: Quantitative DNA methylation levels of Foxp3 promoter in pediatric ITP patients were detected by MassARRAY EpiTYPER. Methylation levels of Foxp3 promoter were analyzed in ITP patients and normal controls.

Results: Significantly higher expression of CpG-2, CpG-3 and CpG-11.12 was observed in ITP patients compared to the controls. A subgroup analysis revealed that persistent and chronic ITP patients exhibited significantly higher CpG-6 expression than in the subgroup of newly diagnosed ITP patients. All patients who represented newly diagnosed ITP at admission were reclassified at later follow-up. In this follow-up subgroup analysis, there were significantly higher levels of CpG-6 in the persistent ITP group than that in the newly diagnosed ITP group.

Conclusions: Our results indicate that defective Treg cell activity identified in ITP might be partially mediated through hypermethylation of CpG sites in the promoter region of Foxp3.

Keywords: Children; DNA methylation; Foxp3; Primary immune thrombocytopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Infant
  • Male
  • Promoter Regions, Genetic*
  • Purpura, Thrombocytopenic, Idiopathic / genetics*
  • Purpura, Thrombocytopenic, Idiopathic / immunology
  • Purpura, Thrombocytopenic, Idiopathic / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors