To support the fundamental ‘Target-to-B!’ program, WP1 aims 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.
In the meantime we have 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).
WP2 is dedicated to set-up specialized assays to study the dynamics, diversity and function of B-lymphocytes in health, B-IMDs and B-ONC. An overview has been generated and the necessary tests have been streamlined to be used to handle samples according to the timing of the protocols decided upon in WP1
WP3 is dedicated to the development and harmonization of assays for structure-function analysis of immunoglobulins and detailed description of (auto)antigen-specific antibody characteristics in relation to clinical phenotype, outcome, and response to antibody- and/or B-cell targeted interventions.
Next to monitoring its scientific and clinical ambition, the consortium also aims to develop an outreach program for multiple stakeholders such as patients, students, clinicians and pharmaceutical industry and the general public.
Communication and exchange of knowledge within and beyond the consortium including patients and general public is embedded in this WP, as well as management issues which will also be supported by a patient-advisory board (PAR).
This WP focuses on the investigation of B-cell differentiation and activation in health and disease over time toidentify common and disease-specific molecular mechanisms involved in the generation and activation of pathogenic B-cells. In this way we will identify biomarkers as common and disease-specific targets with a predictive value to be able to limit or prevent pathogenic B-cell activity and disease.
This WP will focus on the emergence of Fab-glycosylation as a novel, poorly studied layer of antibody and B-cell diversification across diseases . We will study its role in B-cell selection, its significance as a disease-specific diagnostic and prognostic marker, and its physiological functions and effects on antigen-binding over time and the effect of treatment on changes in Fab-glycosylation.
The objective of this WP is to characterize the B-cell (and T-cell) compartment in B-ONC/B-IMD patients before and after therapeutic intervention, using the platform developed in WP2 and WP5, in order to monitor treatment outcome
The effect of antibody removal by IgG depletion via immunoadsorption columns on B-cells activation, plasmacell development and survival is unclear to date. This highly effective depletion of IgG including autoreactive antibodies may have an effect on immune cell composition and activity – to the point of preventing autoimmune disease from developing. We have recently obtained medical ethical approval to now enable us to study the development of autoantibody and an active B cell derived plasmacell pool in this workpackage, fully integrated with clinical outcome data in various B-IMD and autoantibody-associated B-ONC patient groups.