B cell phenotype and function in granulomatosis with polyangiitis: Towards prediction of relapse

Judith Land

    Research output: ThesisThesis fully internal (DIV)

    1500 Downloads (Pure)

    Abstract

    Vasculitis is a term used to indicate a spectrum of disorders that present with inflammation of the blood vessel walls. A subgroup of disorders is characterised by the presence of autoantibodies, the anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV). AAV includes granulomatosis with polyangiitis (GPA).

    GPA patients have a high risk of disease relapse, up to 60% in 5 years. Each relapse affects the quality of life of the patient, and can lead to increased organ damage. When relapses could be predicted it could be possible to prevent relapses through timely intervention.

    Many types of immune cells are involved in GPA, in this thesis we focused on the B cells. The B cell phenotype and function was investigated in healthy controls and GPA patients with and without a relapse, including distribution of different B cell subsets, production of PR3-ANCA IgG and production of pro- and anti-inflammatory cytokines.

    Results included that several differences were found between patients with and without a relapse. In a number of patients, the in vitro production of ANCA increased prior to relapse. Furthermore, there were changes in the B cell subset distribution in GPA patients compared to controls, and these were most pronounced in patients prior to relapse. Before relapse low and decreasing percentages of memory and CD24highCD27+ B cells were seen. Indicating that monitoring the B cell subset distribution could potentially be interesting with regard to relapse prediction. There were also differences in cytokine production, as GPA patients had fewer TNFα producing B cells than controls, and it appeared that IL10 producing B cells may decrease in individual patients prior to relapse.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Heeringa, Peter, Supervisor
    • Stegeman, Coen, Supervisor
    • Rutgers, Bram, Co-supervisor
    • Abdulahad, Wayel, Co-supervisor
    • Bos, Nico, Assessment committee
    • Navis, Gerjan, Assessment committee
    • Little, M. A., Assessment committee, External person
    Award date13-Jun-2016
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-6182-683-1
    Electronic ISBNs978-94-6182-687-9
    Publication statusPublished - 2016

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