Induction of protective immunoglobulin responses in the nasal mucosa
Research type
Research Study
Full title
Supression of local Th2 cytokine response and induction of protective immunoglobulin responses in the nasal mucosa following grass pollen-specific immunotherapy
IRAS ID
131834
Contact name
Mohamed Shamji
Contact email
Sponsor organisation
Imperial College London
Research summary
Seasonal allergic rhinitis (SAR) is the most common allergic disease and affects a quarter of the population in the United Kingdom. Approximately 35% of individuals with SAR have moderate or severe persistent symptoms. This has a serious impact on their quality of life and causes impairment of performance at work or school. Pharmacological treatments may provide symptomatic relief but do not alter the course of the disease.
Grass pollen-specific immunotherapy (SIT) either administered subcutaneously or sublingually (SLIT) is effective in severe seasonal allergic rhinitis. Recent studies suggest that subcutaneous grass pollen immunotherapy results in a 35% decrease in seasonal symptoms, a 54% reduction in rescue medication and a significant improvement of quality of life. The immunological mechanisms of SIT and SLIT involve inhibition of IgE-dependent mechanisms, reductions in recruitment and activation of effector cells including eosinophils, basophils and mast cells at mucosal surfaces. Immunotherapy is associated with induction of IL- 10 producing regulatory T cells. The effect of IL-10 on B cells includes class switching to IgG antibody isotypes, in particular IgG4. These serum antibodies are thought to inhibit basophil histamine release and are able inhibit IgE-mediated responses by preventing cooperative binding of IgE-allergen complexes to trimetric CD23 on the surface of B cells. Despite increasing evidence that grass pollen immunotherapy prevents CD23-dependent allergen-IgE binding to B cells and subsequent presentation to T cells in vitro, there is no evidence that inhibition of CD23-dependent IgE-facilitated allergen presentation occurs in the nasal mucosa.
Primary objective
1. To understand the local and systemic cytokines and allergen-specific immunoglobulin responses following allergen immunotherapy and allergen tolerance in seasonal allergic rhinitis.Secondary objectives
1. To measure differences in local Th2 cytokines, antibody classes and specificities within nasal fluids from atopics, non-atopics and grass pollen SIT patients
2. To determine the inhibitory activity of these fluids using Multiplex luminex and gE-FAB assay, respectively.REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
13/NE/0229
Date of REC Opinion
19 Jul 2013
REC opinion
Favourable Opinion