Periodic Reporting for period 1 - 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)
Berichtszeitraum: 2023-04-01 bis 2025-07-31
Allergic rhinitis (AR) is a widespread chronic condition affecting up to 30% of the global population, with significant impacts on quality of life and healthcare systems. One of the main triggers of AR is the house dust mite (Dermatophagoides pteronyssinus), which provokes immune responses mediated by IgE antibodies. Allergen-specific immunotherapy (AIT) is currently the only treatment capable of modifying the course of IgE-mediated allergies. However, AIT is not effective in all patients, and there are no reliable biomarkers to predict its success.
The PRE-BIT project aims to address this gap by studying the role of B cells—key players in antibody production—in the development of immune tolerance during AIT. Specifically, the project investigates how B cells change their phenotype and antibody production (especially IgG2 and IgG4 isotypes) in response to treatment. By identifying early biomarkers of AIT effectiveness, PRE-BIT seeks to improve patient stratification and treatment outcomes, ultimately contributing to more personalized and cost-effective allergy care.
The PRE-BIT project aims to address this gap by studying the role of B cells—key players in antibody production—in the development of immune tolerance during AIT. Specifically, the project investigates how B cells change their phenotype and antibody production (especially IgG2 and IgG4 isotypes) in response to treatment. By identifying early biomarkers of AIT effectiveness, PRE-BIT seeks to improve patient stratification and treatment outcomes, ultimately contributing to more personalized and cost-effective allergy care.
During the project, a cohort of patients with AR undergoing AIT was recruited and monitored over 12 months. Blood samples were collected at multiple time points and analyzed using advanced techniques such as single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry. These methods allowed the identification of specific B cell subpopulations and their evolution during treatment.
Additionally, ex vivo experiments were conducted to assess how B cells from different patients respond to various cytokine environments, revealing differences in their ability to switch to protective antibody isotypes. The project also explored the diversity and specificity of the B cell receptor repertoire, including the generation of allergen-specific antibodies and their potential to inhibit allergic responses in laboratory models.
Additionally, ex vivo experiments were conducted to assess how B cells from different patients respond to various cytokine environments, revealing differences in their ability to switch to protective antibody isotypes. The project also explored the diversity and specificity of the B cell receptor repertoire, including the generation of allergen-specific antibodies and their potential to inhibit allergic responses in laboratory models.
PRE-BIT has generated novel insights into the immunological mechanisms underlying AIT, particularly the role of B cells in the induction of tolerance. The project identified candidate biomarkers—based on B cell phenotypes and antibody isotypes—that could predict treatment success early in the therapy. These findings pave the way for the development of diagnostic tools to personalize AIT and avoid unnecessary treatments in non-responders.
The methodologies and datasets developed in PRE-BIT are openly shared and can be applied to other allergic diseases beyond AR. Further research and validation in larger cohorts will be essential to translate these findings into clinical practice.
The methodologies and datasets developed in PRE-BIT are openly shared and can be applied to other allergic diseases beyond AR. Further research and validation in larger cohorts will be essential to translate these findings into clinical practice.