CD14 C-159T and early infection with Pseudomonas aeruginosain children with cystic fibrosis

Martin Ac, Zhang G, Laing Ia, Brennan S, Winfield K, Sly Pd, Stick Sm, Goldblatt J, Lesouef, Lesouef Pn

Description

Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P.aeruginosa was subsequently isolated (492.75 μg/ml vs. 1339.43 μg/ml, p = 0.018). Those with the CD14 -159CC genotype had a significantly increased risk of early infection with P.aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P.aeruginosa .

Sujets

• Cystic fibrosis
• CD14
• Pseudomonas aeruginosa

Informations

• Publié par: biomed
• Publié le: 01 janvier 2005
• Nombre de lectures: 9
• Langue: English

Extrait

Respiratory Research

BioMedCentral

Open Access Research CD14 C159T and early infection withPseudomonas aeruginosain children with cystic fibrosis 1,3 1 1 2 2 2,3 AC Martin* , IA Laing , G Zhang , S Brennan , K Winfield , PD Sly , 3 1 1,3 SM Stick , J Goldblatt and PN LeSouef

1 2 Address: School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia 6001, Division of Clinical Science, 3 Telethon Institute for Child Health Research, Perth, Western Australia 6008 and Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia 6008

Email: AC Martin*  [e-mail]; IA Laing  [e-mail]; G Zhang  [e-mail]; S Brennan  [e-mail]; K Winfield  [e-mail]; PD Sly  [e-mail]; SM Stick  [e-mail]; J Goldblatt  [e-mail]; PN LeSouef  [e-mail] * Corresponding author

Published: 23 June 2005 Received: 23 December 2004 Accepted: 23 June 2005 Respiratory Research2005,6:63 doi:10.1186/14659921663 This article is available from: http://respiratoryresearch.com/content/6/1/63 © 2005 Martin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

cystic fibrosisCD14Pseudomonas aeruginosa

Abstract Early acquisition ofPseudomonas aeruginosais associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Fortyfive children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whomP.aeruginosawas subsequently isolated (492.75µg/ml vs. 1339.43µg/ml, p = 0.018). Those with the CD14 159CC genotype had a significantly increased risk of early infection withP.aeruginosasuggesting that CD14 C159T plays a role in determining the risk of early infection withP.aeruginosa.

Introduction Cystic fibrosis (CF) is the most common serious, mono genic, autosomal recessive disease in Caucasians and results from mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CF is characterised by variable phenotypic expression, which is not entirely explained by the allelic heterogeneity of the pathogenic CFTR mutations, and there is accumu lating evidence that much of this phenotypic diversity is due to the effect of modifier genes [1].Pseudomonas aeru ginosa, an environmental organism, is the most important pathogen in patients with CF as chronic infection results

in a more rapid decline in lung function and reduced sur vival [2].

CD14, a key gene of the innate immune system, functions as a receptor for lipopolysaccharide (LPS), a constitutive element of theP.aeruginosacell wall, and is a potential modifier of severity in patients with CF. CD14 is expressed in both a membranebound form on macrophages, monocytes and neutrophils (mCD14) and soluble form in serum (sCD14). A polymorphism in the CD14 gene promoter (C159T) has an allele frequency of approxi mately 50% in Europeans [3]. The 159C allele is associ ated with lower circulating levels of sCD14 in healthy

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