Asthma, Rhinitis, Other Respiratory Diseases
Array-based diagnostic gene-expression score for atopy and asthma

https://doi.org/10.1067/mai.2002.121530Get rights and content

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 for the diagnosis of atopy and asthma and to assess disease activity as a guide for therapeutic decisions. Purified mRNA from PBMCs of 18 atopic asthmatic subjects, 8 atopic nonasthmatic subjects, and 14 healthy control subjects was hybridized to cDNA membranes. A composite atopy gene expression (CAGE) score was determined by using 10 genes dysregulated in atopic individuals according to a specific algorithm. The CAGE score was better than total IgE in differentiating atopic from nonatopic subjects (sensitivity, 96%; specificity, 92%). Correlation between the CAGE score and total IgE (P < .001) was found, and there was a trend for correlation with asthma severity (P = .051). The CAGE score was able to quantify phenotype-specific alteration in gene expression of atopic individuals. The CAGE score might be used as a diagnostic tool or to monitor the effects and side effects of therapy. (J Allergy Clin Immunol 2002;109:271-3.)

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Subjects

Healthy control subjects, atopic nonasthmatic subjects, and atopic asthmatic subjects were recruited. Healthy control subjects were defined as individuals with negative skin prick test results without medication and without lung or systemic disease. Atopy was defined as a positive skin prick test response (wheal of ≥3 mm diameter larger than that produced by the negative control wheal) to a range of 4 common aeroallergens: Dermatophagoides pteronyssinus , cat, dog, and mixed grasses (ALK).

Results

Fourteen nonatopic healthy control subjects (male/ female ratio, 2:12; mean age, 42 ± 13 years; age range, 27-65 years), 8 atopic subjects without asthma (male/female ratio, 7:1; mean age, 36 ± 9 years; age range, 23-49 years), and 18 atopic asthmatic subjects (male/female ratio, 6:12; mean age, 41 ± 14 years; age range, 18-66 years) were included in the study. Sixteen of 18 asthmatic subjects had inhaled corticosteroids and Aas asthma severity scores ranging from 1 to 5 (score 1, n = 2; score

Discussion

In this study we quantified the overall atopy-specific gene-expression activity with the CAGE score. The CAGE score had a sensitivity of 96% and a specificity of 92% for the diagnosis of atopy and thus was superior to total IgE values. The CAGE score correlated with total IgE levels and a trend for asthma severity was found. Thus the CAGE score provided an overall index of current atopic disease activity.

Gene-expression scores could be used as a clear-cut diagnostic tool for the diagnosis and

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Reprint requests: Martin H. Brutsche, MD, PhD, Pneumology, University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland.

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