Complement biology in health and disease

In this thesis several aspects of complement proteins are described, from circulating levels in blood to their intracellular presence and from autoimmunity to the infectious disease tuberculosis. We explored the local production of complement and we describe in Chapter 2 the production of C1q by chondrocytes. Additionally, studies addressing the potential intracellular C3 role are described in Chapter 3. The potential role of the complement system as biomarker was investigated by addressing the presence and concentrations of C1q in serum of patients with active tuberculosis and controls in Chapter 4. Like C1q, we also investigated the expression and concentration of the natural inhibitor C1-INH in Chapter 5. C1q protein was further analysed as biomarker for tuberculosis in experimental non-human primate models in Chapter 6. In this thesis, a newly identified case of a lupus patient is described with a complex medical history and a compound heterozygous deficiency of C1q in Chapter 7. To better comprehend a possible role of a prominent post-translational modification associated rheumatic disease, carbamylation, the interaction between carbamylated IgG was investigated in relation to the ability to activate the complement system. These studies are described in Chapter 8.