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Gene expression in CD4+ T-cells reflects heterogeneity in infant wheezing phenotypes

Depts of ¹ General Paediatrics, ² Dermatology and ³ Paediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands.

CORRESPONDENCE: M. O. Hoekstra, Wilhelmina Children's Hospital, University Medical Centre Utrecht, HP KE 04.133.1, P.O. Box 85090, 3508 AB Utrecht, The Netherlands. Fax: 31 302505349. E-mail: m.o.hoekstra{at}umcutrecht.nl

Keywords: Childhood, gene expression profiles, immunopathology, microarray, wheezing phenotypes

Received: February 10, 2008
Accepted June 30, 2008

Although a marked increase in the reporting of wheezing symptoms since the mid-1970s has been described, the underlying immunopathology of the different wheezing phenotypes has not been clarified. Since differences in gene expression might be involved, the objective of the present study was to identify gene expression profiles in CD4+ T-cells from two distinct infant wheezing phenotypes.

The gene expression profiles of peripheral CD4+ T-cells were compared by means of microarray analysis of six transient wheezers, six persistent wheezers and seven healthy controls. The differentially expressed genes were subsequently validated by RT-PCR.

The differential gene expression profiles reflected common immunological pathways involved in apoptosis or proliferation of T-cells. Furthermore, both wheezing phenotypes showed decreased expression of the complement component 5 receptor 1 gene, a gene involved in the regulation of bronchial responsiveness. Moreover, differences in gene expression profiles were found in genes involved in the immune response against respiratory syncytial virus, such as those encoding signal transducer and activator of transcription 1 and an inflammatory mediator showing enhanced production in asthma (prostaglandin E₂ receptor 2).

The present findings suggest that clinical symptoms of wheeze are reflected in common immunological pathways, whereas differences between wheezing phenotypes are, in part, reflected in distinct gene expression profiles.