Characterization of the IgE Repertoire and Activity in Asthma, V01

• Research type

  Research Study

• Full title

  Genetic and Functional Characterization of the IgE Repertoire and Compartmental Regulation of IgE Activity in the Pathogenesis of Asthma

• IRAS ID

  170356

• Contact name

  Hannah J Gould

• Sponsor organisation

  King's College London

• Duration of Study in the UK

  2 years, 11 months, 31 days

• Research summary

  One in 12 adults and 1 in 5 children in the UK suffer from asthma. Although some medicines do alleviate symptoms they do not cure the disease. The most effective treatment for uncontrolled asthmatics is a synthetic antibody (omalizumab) against the key molecule IgE, itself a type of antibody that primes immune cells in the airways to release mediators that cause asthma in response to inhaled allergens such as grass.

  20% of the most severe “non-atopic” asthmatics are excluded from this treatment because of the assumption that both allergens and IgEs are inextricably linked to the disease, so that, if routine tests for allergen-sensitivity are negative, these patients will not benefit. However, we have shown that IgE is elevated in the blood and airways of “non-atopic” asthmatics and hypothesise that IgE is also involved in their disease, either because the IgEs are against allergens not tested for, or because of allergen-independent mechanisms of IgE activity. We have preliminary evidence for both scenarios, and are planning to explore this further in this project.

  We plan to:
  • ask allergic and non-allergic asthmatics and healthy controls to provide samples of blood and snippets (biopsies) from their upper (nose) and lower (lung) airways for isolation of the IgE-producing cells.
  • compile the IgE repertoire by next generation sequencing and use advanced bioinformatics analyses to track the development and migration of IgE-producing cells.
  • re-create the IgEs made by these patients in the laboratory to study allergen-dependent and independent mechanisms by which the IgEs may cause asthma.

  The knowledge gained will help refine the diagnosis and treatment of asthma. If, for example, we do show IgE to have a role in “non-atopic” asthma, this could pave the way for therapies like omalizumab to become available to and benefit the over 100,000 “non-atopic” asthma patients in the UK.

• REC name

  London - Central Research Ethics Committee

• REC reference

  15/LO/1800

• Date of REC Opinion

  23 Dec 2015

• REC opinion

  Further Information Favourable Opinion