Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab.

Michael Roth,Feng Zhao,Michael Tamm,Didier Lardinois,Jun Zhong,Bernhard Ryffel

doi:10.1371/journal.pone.0136549

Michael Roth, Feng Zhao + Show 4 more

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https://doi.org/10.1371/journal.pone.0136549

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Journal: PloS one	Publication Date: Sep 2, 2015
Citations: 50	License type: CC BY 4.0

Affiliation: University Hospital of Basel, Xijing Hospital

Abstract

BackgroundAirway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix.ObjectiveWe postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.MethodsIsolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.ResultsSerum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.Conclusion and Clinical RelevanceOur data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.

Highlights

Allergies cause approximately 60% of all asthma cases and correlate with increased circulatingIgE levels, which contribute to chronic inflammation [1]
We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix
Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound

Summary

Introduction

Allergies cause approximately 60% of all asthma cases and correlate with increased circulatingIgE levels, which contribute to chronic inflammation [1]. Beside inflammation airway wall remodeling is a leading pathology in asthma and among other factors it is induced by IgE [2, 3]. To counteract the pathologic effects of IgE in atopic asthma humanized anti-IgE antibodies such as Omalizumab have been introduced as a therapeutic concept, and they have been clinically proven to achieve additional beneficial effects on airway wall remodeling compared to standard therapy by inhaled glucocorticoids and long acting β2-agonists [3,4,5]. How the production of these anti-IgE antibodies is induced and if they occur in other allergy diseases needs further investigation This observation supports the concept of therapeutic use of humanized anti-IgE antibodies in allergic asthma and other allergic diseases. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix.

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