Target-2-B!

B cells exert multiple essential functions in our immune system: production of protective antibodies, immunomodulatory cytokines, and antigen-presentation to T cells. Dysregulated activation of B cells forms the basis of a wide variety of B-immune-mediated diseases (B-IMD) characterized by production of disease-causing pathogenic autoantibodies or oncogenic transformation of B cells in various malignancies (B-ONC). The crucial role of B-cells and antibodies in B-IMD/B-ONC pathology is evident from the clinical observation that B-cell and IgG-targeted therapies can be highly effective. We investigate the underlying pathogenic mechanisms in B-IMDs and B-ONCs, their commonalities and differences in functionality of B cell responses and antibodies.

To support the fundamental ‘Target-to-B!’ program, we aim to make a full inventory of existing registries and biobanks, including presence and completeness of clinical data, and whether serial sampling at structured time points has been performed. We have now obtained medical-ethical approval to prospectively collect data and materials for collection of clinical data and the necessary materials for some of the relevant question related to B cell immunity in patients with a variety of different autoantibody-mediated diseases or smouldering B cell associated malignancies (in particular follicular lymphoma and CLL).

Our members performing research in our workpackage dedicated to set-up specialized assays to study the dynamics, diversity and function of B-lymphocytes in health, B-IMDs and B-ONC has successfully validated all necessary assays on B cell differentiation, B cell repertoire analysis (BCR sequencing), deep B cell phenotyping via multiparameter analyses (CyTOF, spectral imaging, flow cytometry). Position papers are being generated and disease-overarching analyses have started. 

Our members performing research in our workpackage dedicated to the development and harmonization of assays for structure-function analysis of immunoglobulins have analysed and compared (auto)antigen-specific antibody characteristics (glycosylation patterns) between diseases and assessed that differences in autoantibody structures exists between patient groups.

he current pandemic with COVID has turned society on its head worldwide. There is a lot of uncertainty. In particular, patients and their practitioners have questions on 1) the impact of SARS-CoV2 infection on their health and autoimmune symptoms and 2) the efficacy of their SARS-CoV2 vaccination when simultaneously taking immune suppressive medication. To get answers to these questions, we submitted as T2B a ZonMW application, which was honored in July 2020 and received again extra funding this year. Health Holland has also granted matching, which makes it possible for our patients to obtain more clarity about COVID in the next two years. The purpose of this ZonMW COVID study is to answer the question of whether the course of SARS-CoV-2-specific immunity differs over time in immune-suppressed patients compared to healthy individuals and whether the efficacy of SARS-CoV-2-targeted vaccination in these patients in the coming year will be similar to that in healthy individuals. SARS-CoV-2 specific B/T cells and antibody assays have been set up in the last 10 months and the multicenter, national vaccination study in different patient cohorts has been started, with a high rate of patient accrual into the study.

Find out more about the consortium on their website.

Collaborators