title: Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated residual chloride secretion does not protect against early chronic Pseudomonas aeruginosa infection in F508del homozygous cystic fibrosis patients.
abstract: Cystic fibrosis (CF) disease severity is characterized by a broad variability that has been attributed, in addition to the CF transmembrane conductance regulator (CFTR) genotype, to modulating factors such as CFTR-mediated residual chloride (Cl-) secretion. Moreover, CFTR has been suggested to function as a receptor for Pseudomonas aeruginosa (PA). In this study, we investigated whether or not the presence of residual Cl- secretion protects against early chronic PA colonization of patients' airways. Excluding influences on the phenotype caused by different CFTR mutations, we evaluated a cohort of F508del homozygous individuals with respect to the correlation between residual Cl- secretion and the age of onset of PA colonization as an important marker of clinical phenotype. A group with early chronic PA colonization before the age of 7 y (n = 14) was compared with a cohort that had no initial PA detection at least until the age of 13 y (n = 10). We determined the Cl- transport properties by using the intestinal current measurement in rectal suction biopsies. Residual Cl- secretion, most likely due to the CFTR Cl- channel, was observed in 63% of subjects, more frequently in early chronically PA colonized than among late or not colonized patients. These results demonstrate the presence of some active F508del-CFTR in the apical cell membrane and imply that factors other than the CFTR-mediated residual Cl- secretion determine the age of onset of PA colonization.
authors: Medizinische Hochschule Hannover, Department of Pediatrics, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany. derichs.nico@mh-hannover.de
authors: Nico
authors: N
authors: Derichs
authors: Frauke
authors: F
authors: Mekus
authors: Inez
authors: I
authors: Bronsveld
authors: Jan
authors: J
authors: Bijman
authors: Henk J
authors: HJ
authors: Veeze
authors: Horst
authors: H
authors: von der Hardt
authors: Burkhard
authors: B
authors: Tummler
authors: Manfred
authors: M
authors: Ballmann
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000378:metabolism*; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism*; D004594:Electrophysiology; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011552:Pseudomonas Infections / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D012129:Respiratory Function Tests
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator