Monocyte and macrophage heterogeneity in Giant Cell Arteritis and Polymyalgia Rheumatica: central in Pathology and a Source of Clinically Relevant Biomarkers

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are chronic inflammatory diseases that frequently overlap and often require long-term treatment with prednisolone. Prednisolone is a drug that suppresses the immune system, but also has serious side effects. GCA and PMR patients suffer from inflammation in their arteries (vasculitis) and joints, respectively. White blood cells such as macrophages play a major role in the initiation and continuation of inflammation. To find new clues for treatment, this thesis focuses on the involvement of macrophages, and on their blood monocyte precursors in these diseases. Both monocytes and macrophages consist of various subtypes that can be distinguished by phenotype (the way they look) and function (the way they behave). We implicated macrophage subtypes, and their likely monocyte precursors, in the development of vasculitis and destruction of the arterial wall. Macrophages in affected tissues also release numerous factors, which can be measured in the blood of patients. We discovered that one of these factors, angiopoietin-2, could aid in detecting vasculitis (GCA) in PMR patients. This is important for patients as GCA is associated with severe complications such as vision loss and aortic rupture. Using these factors in follow-up studies of patients also revealed that the disease may be still ongoing in affected tissues, despite treatment with prednisolone. Finally, we also discovered a profile of factors in the blood that could predict whether GCA and PMR patients require short- or long-term treatment with prednisolone, thereby reducing the side effects in individual patients.