Whole transcriptome sequencing identifies increased CXCR2 expression in PNH granulocytes

Br J Haematol. 2017 Apr;177(1):136-141. doi: 10.1111/bjh.14502. Epub 2017 Feb 1.


The aetiology of paroxysmal nocturnal haemoglobinuria (PNH) is a somatic mutation in the X-linked phosphatidylinositol glycan class A gene (PIGA), resulting in global deficiency of glycosyl phosphatidylinositol-anchored proteins (GPI-APs). This study applied RNA-sequencing to examine functional effects of the PIGA mutation in human granulocytes. CXCR2 expression was increased in GPI-AP- compared to GPI-AP+ granulocytes. Macrophage migration inhibitory factor, a CXCR2 agonist, was significantly higher in plasma of PNH patients. Nuclear factor-κB phosphorylation was upregulated in GPI-AP- compared with GPI-AP+ granulocytes. Our data suggest novel mechanisms in PNH, not obviously predicted by decreased production of the GPI moiety.

Keywords: CXCR2; RNA-sequencing; paroxysmal nocturnal haemoglobinuria.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Case-Control Studies
  • Cluster Analysis
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Granulocytes / metabolism*
  • Hemoglobinuria, Paroxysmal / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Receptors, Interleukin-8B / genetics*
  • Transcriptome*


  • Biomarkers
  • Receptors, Interleukin-8B