Macrophage diversity in the pathogenesis of vasculitides: implications for diagnosis and treatment

    Research output: ThesisThesis fully internal (DIV)

    133 Downloads (Pure)

    Abstract

    Giant cell arteritis (GCA) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are diseases marked by inflammation of blood vessels. Vascular damage occurring from GCA can lead to various severe complications such as blindness, stroke, and aortic dissection, while vascular damage from AAV often leads to organ malfunction such as kidney failure, leading to increased morbidity and mortality of the patients. Both GCA and AAV are marked by systemic inflammation and massive local leukocyte infiltration at the site of inflammation. In both diseases, macrophages account for the majority of infiltrating leukocytes – affirming their importance in the development of these diseases and making them attractive cellular markers for disease progression and treatment response. Macrophages can change their phenotypes depending on signals from the microenvironment. A deeper understanding of the macrophage phenotypes and their roles in the progression of vasculitides would allow us to exploit their heterogeneity therapeutically to specifically target proinflammatory macrophages. At the same time, this may aid the identification of markers suitable for diagnostic purposes and follow-up assessment. However, to date, our knowledge of macrophage heterogeneity in the pathogenesis of vasculitides is limited. This thesis identified distinct macrophage populations associated with distinct functions pertaining to the development of GCA and AAV. Additionally, soluble factors shed by these macrophages may aid in disease diagnosis and monitoring. Last but not least, we discussed the vast possibilities of specifically targeting these macrophages for the purpose of disease monitoring and treatment.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Brouwer, Liesbeth, Supervisor
    • Heeringa, Peter, Supervisor
    • Slart, Riemer, Supervisor
    • Boots, Mieke, Supervisor
    Award date10-Nov-2021
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-6421-523-6
    Electronic ISBNs978-94-6421-524-3
    DOIs
    Publication statusPublished - 2021

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