PRE-BIT
Understanding the role of B cell phenotypes as a predictor of the efficacy and prognosis of allergen immunotherapy using allergic rhinitis to house dust mite as a model
Financed by: European Union
Programme: Horizon Europe Marie Sklodowska-Curie Actions (MSCA)
Topic: HORIZON-MSCA-2022-PF-01-01 MSCA Postdoctoral Fellowships 2022
Grant agreement ID: 101105416
Estimated starting date: 01/04/2023
Estimated end date: 31/03/2025
Beneficiary: Carlos José Aranda Clemente
Supervisor: Cristobalina Mayorga Mayorga
Implementation centre: Hospital Regional Universitario de Málaga & IBIMA Plataforma Bionand
Research group of IBIMA involved: Drug and Allergen Allergic Diseases
Abstract
Allergic rhinitis (AR) is one the more prevalent respiratory allergic disease affecting 20-30% of the global population. The inflammatory process is mediated by eosinophil infiltration and IgE secreted by plasma cells. IgE is a key component in allergies so understanding IgE production and its inhibition is important for treating these diseases. Allergen immunotherapy (AIT) is the only treatment that targets the etiology of allergic diseases.
However, the efficacy of the treatment reaches 70-80% in the best scenarios (lower for food allergy), it has a high cost, and most important, prediction of the effectiveness of the treatment is not possible with actual biomarkers. In this proposal the candidate seeks to better understand the phenotypes of B cells, key cells implicated in allergy that are modified with AIT. The knowledge generated by this study will provide biomarkers of AIT prognosis and even predict the outcome of the therapy by analyzing the B cell compartment in patients candidate for AIT. Using very innovative approaches, we will analyze the B cell repertoire involved in the resolution of AR through AIT. B cell repertoire will be analyzed in bulk before and after AIT.
In addition, antigen specific B cells will be immortalized so the antibody sequence as well as reactivity can be studied. Moreover, we will perform an ex vivo class switch assay that could potentially predict the outcome of AIT using cytokine microenvironments like those produced by the therapy and or the pathogenic situations. B cell switching from IgD/M or IgG1 to IgG2/4 appears to be a critical step in the effectiveness in AIT because IgE memory resides in the IgG compartment. We will use AR to house dust mite patients as a model as it is one of the most prevalent allergic diseases.
