Immunoglobulin (Ig)E Expression Pattern in Lung: Relation to Systemic IgE and Asthma Phenotypes

Background: Immunoglobulin E (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 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 over 90 subjects with eosinophilic (SAeo + ) and non-eosinophilic (SAeo − ) severe asthma, mild asthma and normal subjects were immunostained for IgE, signal-amplifying isoform of IgE receptor (Fc ε RI β ) and markers of mast cells, eosinophils and lymphocytes. Tissue expression of IgE, Fc ε RI β , 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. While the groups were similar in systemic/serum IgE and atopy, local/tissue IgE was highest in SAeo+ and correlated with eosinophils and lymphocytes (r s =0.52; p<0.0001 and r s =0.23; p=0.03, respectively). Higher local IgE was associated with better lung function, but also with more severe exacerbations of asthma. Capsule Summary: The study reports mucosal distribution of mast cell-bound IgE in human lung and suggests that local IgE and related responses rather than systemic/serum IgE and atopy are more relevant in determining clinical outcomes in asthma.

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