Endotypes of severe allergic asthma patients who clinically benefit from anti-IgE therapy

Yu Chen Huang, Chih Ming Weng, Meng Jung Lee, Shu Min Lin, Chun Hua Wang, Han-Ping Kuo*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

28 Scopus citations

Abstract

Background: Omalizumab, a recombinant monoclonal anti-IgE antibody, was developed for the treatment of severe allergic asthma. Not all these patients respond to omalizumab. Objective: This study aimed to evaluate whether the proinflammatory cytokine profiles in the severe allergic asthma patients were different between who responded and nonresponded to omalizumab therapy. Methods: A prospective study was conducted to examine type 2 cytokines and epithelium-derived cytokines in the bronchial tissues by immunohistochemistry, Western blot and PCR analysis among patients with severe allergic asthma before and after omalizumab therapy. Results: Fourteen of 23 patients with unstable severe allergic asthma improved their asthma control after 4 months of omalizumab treatment (Responders), while nine failed to improve (Non-Responders). Most of Responders were type 2-high endotype (12/14) with upregulated expression of IL-33, IL-25 and TSLP in their bronchial tissues, while most of Non-Responders were type 2-low endotype (8/9). Repeated bronchoscopic biopsy was done in nine responders after omalizumab treatment and showed a decline in IL-13, IL-33, IL-25 and TSLP expression in the bronchial tissues. Among 14 Responders who continued omalizuamb treatments to a total 12 months, six patients achieved a well control of asthma (ACT ≥ 23), while eight patients required additional treatment for asthma symptoms and had more rhinosinusitis comorbidities and a mixed eosinophilic and neutrophilic inflammation in their bronchial tissues. Conclusion: Most of the severe allergic asthma patients who benefited from omalizumab treatment were IL-33, IL-25 and TSLP aggravated type 2-high endotype. Rhinosinusitis or with a mixed eosinophilic and neutrophilic airway inflammation should be evaluated in patients who partially responded to omalizumab treatment.

Original languageEnglish
Pages (from-to)44-53
Number of pages10
JournalClinical and Experimental Allergy
Volume49
Issue number1
DOIs
StatePublished - 01 2019

Bibliographical note

Publisher Copyright:
© 2018 John Wiley & Sons Ltd

Keywords

  • IL-25
  • IL-33
  • IgE
  • anti-IgE
  • severe asthma
  • thymic stromal lymphopoietin
  • type 2 cytokines

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