Description du projet
Biomarqueurs de l’immunothérapie allergénique
La rhinite allergique (RA) est une maladie allergique provoquée par une réaction excessive du système immunitaire aux particules en suspension dans l’air, comme le pollen et les acariens. L’immunothérapie allergénique (ITA) est un type de traitement des troubles allergiques qui consiste à injecter de petites quantités d’un extrait d’allergène sous la peau au cours d’une période donnée afin de réduire la gravité des symptômes en désensibilisant le système immunitaire du patient à l’allergène. Financé par le programme Actions Marie Skłodowska-Curie, le projet PRE-BIT se propose d’étudier les phénotypes des cellules B modifiées par l’ITA et de générer des biomarqueurs capables de prédire les résultats de la thérapie. Les chercheurs analyseront le compartiment des cellules B chez les patients souffrant de RA avant et après l’ITA et identifieront les biomarqueurs associés à l’efficacité de cette immunothérapie.
Objectif
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.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
29590 MALAGA
Espagne