Original article: Omalizumab decreases nonspecific airway hyperresponsiveness in vitro

In asthmatic patients, both symptoms and hyperresponsiveness are related to immunoglobulin E (IgE) concentration in serum. The anti-IgE monoclonal antibody omalizumab improved the control of asthma, but its effect on airway hyperresponsiveness is controversial. Passive sensitization reproduced in vi...

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Veröffentlicht in:Allergy (Copenhagen) 2007-02, Vol.62 (2), p.154
Hauptverfasser: Berger, P, Scotto-Gomez, E, Molimard, M, Marthan, R, V. Le Gros, Tunon-de-Lara, J M
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Sprache:eng
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Zusammenfassung:In asthmatic patients, both symptoms and hyperresponsiveness are related to immunoglobulin E (IgE) concentration in serum. The anti-IgE monoclonal antibody omalizumab improved the control of asthma, but its effect on airway hyperresponsiveness is controversial. Passive sensitization reproduced in vitro a bronchial hyperresponsiveness, an increase in IgE bearing cells, and a mast cell degranulation. This study was designed to examine the effect of omalizumab on passive sensitization-induced hyperresponsiveness, alterations in IgE positive inflammatory cells and mast cell degranulation within the bronchial wall. Proximal (3-5 mm diameter) and distal (0.5-1.5 mm diameter) human bronchi dissected out from 10 lung specimens were incubated in normal or asthmatic serum containing various concentrations of omalizumab. Contractile responses to histamine or Dermatophagoides pteronyssinus (D. pter ) were recorded using an organ bath system and expressed as percentage of maximal contractile response to acetylcholine (ACh). Immunohistochemistry was performed using monoclonal antibodies directed against IgE or tryptase. Mast cells were classified as fully granulated (type I), partly (type II) or largely degranulated (type III). The specific bronchial hyperresponsiveness to D. pter and the nonspecific bronchial hyperresponsiveness to histamine following passive sensitization were significantly inhibited by omalizumab in both distal and proximal airways. Passive sensitization-induced increase in IgE positive cells was also abolished by omalizumab in a concentration dependent manner. Mast cell degranulation which was inhibited by omalizumab was positively correlated with the contractile response to D. pter. Omalizumab blocks specific and nonspecific bronchial hyperresponsiveness. Anti-IgE also decreases IgE bearing cell number and mast cell degranulation. [PUBLICATION ABSTRACT]
ISSN:0105-4538
1398-9995
DOI:10.1111/j.1398-9995.2006.01243.x