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Topics of the month
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3. Outline WP3 by Nico Bos
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Our project
Target to B has been formed to investigate B- cell immune mediated diseases characterized by production of pathogenic autoantibodies or oncogenic transformation of B-cells in various malignancies. Our ambition is
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- to integrate and expand current knowledge on these diseases,
- to establish a harmonized immune monitoring platform and
- to provide mechanistic understanding to predict outcome and develop innovative treatment modalities.
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B-cells are an essential arm of adaptive immunity-in-balance, as their differentiation in response to foreign antigen generates protective immunological memory and antibodies. When out of balance, aberrant B-cell differentiation and escape from immunological checkpoints governing tolerance and B-cell-selection/activation may lead to pathological, autoreactive, immunological memory and (auto)antibodies. As a result a wide array of immune-mediated diseases (B-IMDs) or malignant transformation of B-cells may follow.
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Our consortium represents a national interdisciplinary platform that combines basic and translational B-cell research aiming to understand B-cell derailment and to improve B-cell-targeted therapies in partnership with industry and a patient-advisory-board
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Since almost 10% of the population suffers from either IMDs or lymphoma/leukemia in the Netherlands, there is urgent need for combining B-cell biology expertise across disease fields to optimize therapy efficacy within the fields of B-IMDs and B-cell/plasmacell malignancies. Oncological experience will cross-fertilize and improve IMD treatment approaches possibly leading to cure. IMD-derived B-cell knowledge will fuel development of new treatment strategies in oncology.
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“10% of the population suffers from either IMDs or lymphoma/leukemia in the Netherlands.”
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I’m Maartje Huijbers and I work as a senior scientist at the department of Neurology and the department of Human Genetics of the LUMC. Together with prof. Jan Verschuuren I’m one of the work package 1 leaders were we aim to generate a large database of patient material and patient data to facilitate cross-specialism research under the Target-to-B consortium.
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We’re furthermore going to investigate the immunological features of autoimmune diseases that are caused by predominant IgG4 autoantibodies.
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Senior Scientist Neurology
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and Human Genetics of the LUMC
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Biomedical Sciences (BSc)
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at the University of Amsterdam
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My name is Dorit Verhoeven, I am 26 years old and I live in Amsterdam. First, I studied Biomedical Sciences (BSc) at the University of Amsterdam and after that I did a fast-track Medicine Master (SUMMA/MSc) at the University of Utrecht. In december I started my PhD within the the ‘Target-to-B!’ program to study B-cell dysregulation within the group of prof. Taco Kuijpers at the Experimental Immunology Department at the AMC.
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Our aim is to identify and study target proteins involved in B-cell development into plasmacells using gene editing techniques such as CRISPR-Cas9 towards prevention strategies or therapies for B-cell mediated immune diseases
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Outline WP3
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Biomedical Sciences (BSc)
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at the University of Amsterdam
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“In workpackage 3 we try to understand the impact of B cell targeted therapy on the repertoire of autoantibodies with respect to different subclasses of IgG, isotypes and Fab-glycans. Most therapies will suppress all B cells, but we don’t know if the same or different auto-antibody producing B cells return after stopping the treatment. We have selected 5 autoimmune diseases to start with to compare the dynamics of autoantibody characteristics over time during and after treatment. Since this question closely relates to workpackage 6 that focuses on the role of Fab glycans in B cell autoimmunity, we have joined forces and analyze both isotypes, subclass and Fab glycoylation in the same samples.
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We have selected ANCA vasculitis, Phemphigus, GBS, Myastenia gravis and ACPA-RA as the first auto-immune diseases to start off with and all researchers have agreed to submit samples to the study. The workflow is that all samples will be shipped to Sanquin where the team of Theo Rispens will separate the serum samples into a SNA+ and a SNA- fraction and both fractions will be returned to the centers where they came from. On both fractions and the unseparated samples an isotype and subclass-specific autoantibody assay will be performed. The first samples have arrived at Sanquin and in the coming weeks the rest will follow. We are excited that we are getting the ball running now and we look forward to the results of these unique comparisons in the near future.”
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