Abstract
Age-related alterations of the immune system may contribute to the development of autoimmune diseases. This thesis aimed to explore phenotypical and functional changes in the innate arm of the immune system during the ageing process in healthy individuals as well as in systemic vasculitides including anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (AAV), giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) which occur in elderly only. AAV is a life-threatening, small vessel vasculitis frequently affecting the upper and lower respiratory tract and kidneys, while GCA is a granulomatous vasculitis which mainly affects the medium and large arteries causing vascular occlusion leading to blindness or stroke. PMR is a rheumatic disease characterized by pain and stiffness of both shoulders and hips and by systemic inflammation which frequently co-occur with 50% of GCA patients.
In this thesis, we confirm that age related changes in the innate arm of the immune system contribute to disease severity in an AAV animal model. Next, we describe how ageing affects the phenotype and cytokine responses of immune cells in healthy individuals. We found that CD16+ monocytes increase with age and produce more pro-inflammatory cytokines. These pro-inflammatory monocytes are likely the precursors of vascular inflammatory macrophages in GCA. Moreover, the potential of these monocytes as biomarkers of a relapse in PMR patients is reported. These findings may provide a rational towards novel treatment options and may help the identification of highly awaited, disease-specific biomarkers in GCA and PMR.
In this thesis, we confirm that age related changes in the innate arm of the immune system contribute to disease severity in an AAV animal model. Next, we describe how ageing affects the phenotype and cytokine responses of immune cells in healthy individuals. We found that CD16+ monocytes increase with age and produce more pro-inflammatory cytokines. These pro-inflammatory monocytes are likely the precursors of vascular inflammatory macrophages in GCA. Moreover, the potential of these monocytes as biomarkers of a relapse in PMR patients is reported. These findings may provide a rational towards novel treatment options and may help the identification of highly awaited, disease-specific biomarkers in GCA and PMR.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 7-Sep-2016 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-94-6182-713-5 |
| Electronic ISBNs | 978-94-6182-713-5 |
| Publication status | Published - 2016 |