Array-based diagnostic gene expression score for atopy and asthma
M. H. Brutsche, L. Joos, I. E. A. Carlen Brutsche, L. Hadley, P. Wood, A. Custovic, A. Woodcock (Basle, Switzerland; Manchester, United Kingdom)
Source: Annual Congress 2001 - Molecular and cellular pathology of asthma
Session: Molecular and cellular pathology of asthma
Session type: Poster Discussion
Number: 3556
Disease area: Airway diseases
Abstract Whether gene expression is useful in discriminating different atopic phenotypes is unclear. The aim of the study was to evaluate a gene expression score to diagnose atopy and asthma. Eighteen atopic asthmatics (AA), 8 atopic non-asthmatic (AN) and 14 healthy control subjects (C) were included in the study. Purified mRNA from PBMCs was reverse-transcribed and hybridized to cDNA membranes (ATLAS™ Human cDNA array, Clontech, Palo Alto, USA). Group differences of half of the subjects were assessed with the Mann-Whitney U-test. Differentially expressed genes were used to formulate a composite atopy gene expression (CAGE) score and tested in the second half of the subjects with regard to asthma severity/systemic effects of ICS. ROC analysis was performed to test the effectiveness of CAGE, total IgE and age in differentiating AN and AA from C in terms of gene expression. AN and AA had significantly different CAGE scores compared to C (both p=0.001).The CAGE score was able to differentiate atopic from non-atopic subjects (sensitivity/specificity 100/83%). The CAGE score (area=0.987; p<0.001) was more able to differentiate then total IgE (area=0.854; p=0.001). Correlation between the CAGE score and both total IgE (p= 0.035) and asthma severity (by Aas score) was found (p=0.009). The CAGE score quantitates overall atopy-specific alteration in gene expression and thus atopy-specific gene expression activity. It correlates with asthma severity and total IgE levels and is better in discriminating atopic from non-atopic individuals then IgE. Proof of concept was produced for the usefulness and performance of a phenotype gene expression score.
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M. H. Brutsche, L. Joos, I. E. A. Carlen Brutsche, L. Hadley, P. Wood, A. Custovic, A. Woodcock (Basle, Switzerland; Manchester, United Kingdom). Array-based diagnostic gene expression score for atopy and asthma. Eur Respir J 2001; 16: Suppl. 31, 3556
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