Bacterial infection and ANCA-associated vasculitis: connecting mechanisms

ANCA-associated vasculitides are a group of chronic, autoimmune mediated inflammatory disorders characterised by the presence of anti-neutrophil cyoplasmic autoantibodies (ANCA). When untreated, the disease progresses fast and will cause severe damage to the airways and kidneys. Although the disease mechanisms are increasingly being understood, it is still unclear why certain people develop autoimmunity. Likely a certain genetic background is involved. Also there are indications that bacterial infection could play a role. The focus of this thesis was on mechanisms involved. First, it was investigated whether or not antibodies against complementary Proteinase-3 are present in patients with PR3-ANCA associated vasculitis. Furthermore, the possible role of Toll-like receptors was investigated. Toll-like receptors are important detectors of bacterial proteins and DNA, and we studied the expression of these receptors in white blood cells from patients with ANCA-associated vasculitis. In addition, the capacity of bacterial proteins to stimulate the production of ANCA was studied.