B cells in ANCA-associated vasculitides: from pathogenic players to biomarkers

Anouk von Borstel

    Research output: ThesisThesis fully internal (DIV)

    864 Downloads (Pure)

    Abstract

    Granulomatosis with polyangiitis (GPA) is a systemic autoimmune disease characterized by inflammation of small- to medium-sized blood vessels. Although the disease etiology is largely unknown, activated T- and B-cells are thought to play important roles in the disease pathogenesis. In this thesis we studied the role of B-cells in the GPA pathogenesis and whether monitoring of these cells in peripheral blood of GPA patients can predict disease relapses.
    We studied whether B-cells are intrinsically different in their capacity to respond to B-cell receptor stimulation. This study showed that B-cells of GPA patients are more sensitive to B-cell receptor stimulation as shown by increased levels of the intracellular protein Bruton’s tyrosine kinase (BTK). Additionally, B-cell activation could be inhibited by blocking BTK activity. This finding is of importance, as it indicates that BTK could be used as a novel therapeutic target to inhibit B-cell activation in GPA patients.
    Another important finding described in this thesis is that an increased frequency of plasmablasts (i.e. a B-cell subset) in the circulation of GPA patients was associated with increased occurrence of disease relapses. These plasmablasts were also found in kidney biopsies and urine of GPA patients with active renal disease, indicating that these cells are directly involved in the autoinflammatory process of GPA.
    Collectively, the work presented in this thesis enhances our knowledge on the role of B-cells in the GPA pathogenesis and describes several new targets for treatment and prediction of disease relapses in GPA.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Heeringa, Peter, Supervisor
    • Stegeman, Coen, Supervisor
    • Sanders, Jan Stephan, Co-supervisor
    • Abdulahad, Wayel, Co-supervisor
    Award date11-Sep-2019
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-1866-7
    Electronic ISBNs978-94-034-1865-0
    DOIs
    Publication statusPublished - 2019

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