Descripción del proyecto
Biomarcadores para la inmunoterapia con alérgenos
La rinitis alérgica (RA) es una enfermedad alérgica que se produce cuando el sistema inmunitario reacciona de forma desproporcionada a partículas transportadas por el aire, como el polen y los ácaros del polvo. La inmunoterapia con alérgenos (ITA) es un tipo de tratamiento de los trastornos alérgicos que consiste en inyectar pequeñas cantidades de un extracto de alérgeno subcutáneo durante un período de tiempo para reducir la gravedad de los síntomas mediante la desensibilización del sistema inmunitario del paciente al alérgeno. El objetivo del proyecto PRE-BIT, financiado por las acciones Marie Skłodowska-Curie, es estudiar los fenotipos de los linfocitos B modificados por la TIA y generar biomarcadores que predigan el resultado del tratamiento. Los investigadores analizarán el compartimento de los linfocitos B en pacientes con RA antes y después de la ITA e identificarán biomarcadores asociados a la eficacia de la ITA.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinador
29590 MALAGA
España