Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor

J Cyst Fibros. 2016 Jan;15(1):67-73. doi: 10.1016/j.jcf.2015.02.010. Epub 2015 Mar 11.


Background: Ivacaftor improves clinical outcome by potentiation of mutant G551D CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils (PMNs), we hypothesized that ivacaftor may impact leukocyte activation.

Methods: We examined blood leukocytes from G551D CF subjects prior to and at one and six months after receiving ivacaftor. Blood leukocytes from ivacaftor-naïve G551D, F508del, and healthy controls were also treated with ivacaftor ex vivo to assess mutation-specific effects.

Results: Compared to healthy controls, G551D CF subjects had significantly higher expression of active CD11b on PMNs and of CD63 on monocytes, which were normalized by in vivo ivacaftor treatment. Ex vivo exposure to ivacaftor of blood cells from G551D, but not F508del and healthy subjects, resulted in changes in CXCR2 and CD16 expression on PMNs.

Conclusions: In vivo and ex vivo exposure of G551D CF leukocytes to ivacaftor resulted in an altered activation profile, suggesting mutation-specific leukocyte modulation.

Keywords: Blood; CFTR; G551D; Ivacaftor; Leukocyte; VX-770.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminophenols / administration & dosage*
  • CD11b Antigen / analysis*
  • Chloride Channel Agonists / administration & dosage
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis* / blood
  • Cystic Fibrosis* / drug therapy
  • Female
  • Humans
  • Male
  • Monocytes* / drug effects
  • Monocytes* / immunology
  • Mutation
  • Neutrophils* / drug effects
  • Neutrophils* / immunology
  • Quinolones / administration & dosage*
  • Statistics as Topic
  • Tetraspanin 30 / analysis*


  • Aminophenols
  • CD11b Antigen
  • CFTR protein, human
  • Chloride Channel Agonists
  • Quinolones
  • Tetraspanin 30
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor