[HTML][HTML] Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor
PE Bratcher, SM Rowe, G Reeves, T Roberts… - Journal of Cystic …, 2016 - Elsevier
PE Bratcher, SM Rowe, G Reeves, T Roberts, T Szul, WT Harris, R Tirouvanziam, A Gaggar
Journal of Cystic Fibrosis, 2016•ElsevierBackground 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 …
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 …
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.
Elsevier