Mechanisms of asthma and allergic inflammation
IgE expression pattern in lung: Relation to systemic IgE and asthma phenotypes

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Background

IgE-mediated responses contribute to allergy and asthma. Little is understood regarding the relationship of tissue IgE to systemic IgE, inflammation or clinical outcomes.

Objectives

To evaluate local IgE expression and cellular inflammation in the proximal and distal lung of normal subjects and subjects with asthma of varying severity and relate those tissue parameters to systemic IgE levels, atopy, lung function, and history of severe exacerbations of asthma.

Methods

Tissue from more than 90 subjects with eosinophilic (SAeo+) and noneosinophilic (SAeo−) severe asthma, mild asthma and normal subjects were immunostained for IgE, signal-amplifying isoform of IgE receptor (FcɛRIβ) and markers of mast cells, eosinophils, and lymphocytes. Tissue expression of IgE, FcɛRIβ, cellular inflammation, serum IgE, and atopy were compared. Regression models were used to determine the relationship of local and systemic IgE to lung function and severe exacerbations of asthma.

Results

Mast cell–bound IgE was present along airways but absent in lung parenchyma. Although the groups were similar in systemic/serum IgE and atopy, local/tissue IgE was highest in SAeo+ and correlated with eosinophils and lymphocytes (rs = 0.52, P < .0001; and rs = 0.23, P = .03, respectively). Higher local IgE was associated with better lung function, but also with more severe exacerbations of asthma.

Conclusion

Local IgE appears to be primarily a component of responses within the mucosal immune compartment and is related to cellular inflammation, lung function, and clinical outcomes in asthma.

Clinical implications

Local/airway IgE-related processes rather than systemic markers of atopy may be relevant in determining clinical outcomes in asthma.

Section snippets

Subjects

Subjects' asthma severity was determined using previously published criteria.14 Subjects with severe asthma were further subgrouped into those with tissue eosinophilia (SAeo+; >22 eosinophils/mm2 tissue, equivalent to ≥2 × SD from the mean value measured in normal controls) or without (SAeo−), as previously reported.14 The details are in this article's Online Repository at www.jacionline.org.

This study also included 5 healthy organ donors' lung samples. The lungs, which were procured but not

Subjects

Forty-seven subjects with severe asthma (21 SAeo+ [81% atopic] and 26 SAeo− [75% atopic]), 20 subjects with mild asthma (MAs, 85% atopic) and 23 normal subjects (NC, 77% atopic) were evaluated (see this article's Table E1, including data on asthma exacerbations, in the Online Repository at www.jacionline.org). The atopic status among the 4 groups was similar (P = .87). Fourteen SAeo+ and 19 SAeo− were on oral corticosteroids alone or in addition to a high dose of inhaled corticosteroids,

Discussion

This study is the first to present a comprehensive evaluation of local IgE expression throughout the human lung in tissue samples from more than 90 subjects with and without asthma, as well as the first evaluation of tissue expression of the tetrameric/signal-amplifying isoform of the high-affinity IgE receptor. The results demonstrate preferential expression of IgE in the airway submucosa as compared to the lung parenchyma and only a limited relationship of local/mucosal IgE expression with

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    Supported by National Institutes of Health grants HL-64087, AI-40600, and RR-00051; American Lung Association of Colorado, Oklahoma, and Alaska; and Genentech Inc.

    Disclosure of potential conflict of interest: S. Balzar has received grant support from Genentech. S. E. Wenzel has consulting arrangements with Genentech, has received grant support from Genentech, and is on the speakers' bureau for Genentech. The rest of the authors have declared that they have no conflict of interest.

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    Copyright © 2007 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.