Descrizione del progetto
Biomarcatori dell’immunoterapia allergene-specifica
La rinite allergica è una malattia allergica causata da una reazione eccessiva del sistema immunitario alle particelle presenti nell’aria, come pollini e acari della polvere. L’immunoterapia allergene-specifica (AIT, Allergen Immunotherapy) è un tipo di trattamento per i disturbi allergici che prevede l’iniezione sottocutanea di piccole quantità di un estratto di allergene per un certo periodo di tempo, al fine di ridurre la gravità dei sintomi desensibilizzando il sistema immunitario del paziente all’allergene. Finanziato dal programma di azioni Marie Skłodowska-Curie, il progetto PRE-BIT intende studiare i fenotipi delle cellule B modificate dall’AIT e generare biomarcatori in grado di prevedere l’esito della terapia. I ricercatori analizzeranno il compartimento delle cellule B nei pazienti con rinite allergica prima e dopo l’AIT e identificheranno i biomarcatori associati all’efficacia dell’AIT.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
29590 MALAGA
Spagna