Original Articles: Mechanisms of Allergy
Local expression of ϵ germline gene transcripts and RNA for the ϵ heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma

https://doi.org/10.1067/mai.2001.114339Get rights and content

Abstract

Background: The demonstration of ϵ germline gene (Cϵ) transcripts and mature mRNA for the ϵ heavy chain gene (Iϵ) in the nasal mucosa suggested that IgE synthesis may occur in allergic rhinitis. Objective: In view of our previous demonstration of increases in IL-4 mRNA+ cells in asthmatic subjects, we assessed whether local IgE synthesis may also be a feature of bronchial asthma. Methods: Fiberoptic bronchoscopic mucosa biopsy specimens were obtained from 9 atopic asthmatic subjects and 10 nonatopic normal (intrinsic) control subjects. To control for atopy, we also studied 9 nonatopic asthmatic subjects and 10 atopic nonasthmatic control subjects. Tissue was processed for immunohistochemistry for B cells (CD20) and in situ hybridization for Iϵ and Cϵ RNA+ cells and IL-4 mRNA+ cells. Results: B-cell numbers in the bronchial mucosa were similar for asthmatic subjects compared with control subjects, whereas significantly higher numbers of Iϵ RNA+ (P = .02 and P = .04, respectively), Cϵ RNA+ (P = .01 and P = .03, respectively), and IL-4 mRNA+ (P = .001 and P = .001, respectively) cells were observed in atopic asthmatic subjects and nonatopic asthmatic subjects, respectively, but not in atopic control subjects compared with nonatopic control subjects. In asthmatic subjects there were significant correlations between Iϵ RNA+ cells (r = 0.54, P = .02) and Cϵ RNA+ cells (r = 0.48, P = .05) when compared with the number of IL-4 mRNA+ cells. Conclusion: Increases in Iϵ and Cϵ RNA+ cells, but not B-cell numbers, in the bronchial mucosa provide evidence for local IgE synthesis in both atopic and nonatopic asthma. These changes appear to relate to asthma rather than atopy per se and, at least in part, may be under the regulation of IL-4. (J Allergy Clin Immunol 2001;107:686-92.)

Section snippets

Patients

The study was performed with the approval of the Ethics Committees of the Royal Brompton Hospital (London, United Kingdom) and the Hochgebirgsklinik (Davos Wolfgang, Switzerland). Written informed consent was obtained.

Bronchial biopsy specimens were taken from atopic asthmatic subjects and nonatopic control subjects. We also included a group of nonatopic asthmatic subjects and atopic nonasthmatic control subjects (Table I).11

. Clinical features of study participants

Empty CellAtopic asthmatic subjectsEmpty Cell

Results

Individual CD20+ B lymphocytes were seen scattered throughout the bronchial mucosa, mainly within the lamina propria, as discreet individual cells rather than cell aggregates (Fig 1, A ). There was a wide scatter from 0 to 90 cells/mm2 in both atopic and nonatopic asthmatic subjects and in atopic and nonatopic healthy subjects, with no significant differences among the groups (Table II).

Cells expressing RNA for the sterile ϵ germline gene transcript (Iϵ) and mature RNA for the ϵ heavy chain

Discussion

In patients with bronchial asthma compared with normal control subjects, despite comparable numbers of CD20+ B lymphocytes within the bronchial mucosa, we detected elevated numbers of cells expressing the ϵ germline gene transcript (Iϵ) and cells expressing Cϵ, which detects either the sterile transcript or mature ϵ heavy chain messenger RNA. These elevations were detected in biopsy specimens from both atopic and nonatopic asthmatic subjects but not in biopsy specimens from atopic nonasthmatic

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    Reprint requests: Stephen R. Durham, MD, Upper Respiratory Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse St, London SW3 6LY.

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