Properdin-dependent activation and control of immune-homeostasis and autoimmunity

O'Flynn, J. (2014)

Doctoral Thesis

The complement system has been shown to have a role in various systemic autoimmune (AI) diseases which have a renal component. This includes systemic lupus erythematosus (SLE), goodpastures syndrome and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides. In particular the classical pathway (CP) of complement is involved in SLE, with the exact mechanism of how these SLE autoantigens along with their autoantibodies interact with complement in the glomerulus remaining ambiguous. Furthermore, recent studies have demonstrated the expanding role of the alternative pathway (AP) of complement activation in steady state or in aspects of ANCA associated vasculitides or anti-GBM disease. The precise means of activation of the AP in these immune complex mediated disease settings remains unclear. Regulation is imperative in the AP due to its inherent ability to autoactivate. Factor H and properdin are both key opposing regulators in the AP with novel emerging roles in initiation and control of the AP. Deciphering the specific modes of AP activation and involvement is an ever expanding field requiring further elucidation, with previously unexpected roles for AP components revealing the diversity and complexity of this ancient pathway.

• ANCA
• Anti-GBM
• SLE
• Autoimmunity
• Alternative pathway
• Factor H
• Complement
• Properdin

• All authors: O'Flynn, J.
• Supervisor: Kooten, C.van
• Co-supervisor: Daha, M.R.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine (LUMC), Leiden University
• Date: 2014-08-28
• ISBN (print): 9789053358900
• Sponsorship: Dutch Kidney Foundation, Astellas Pharma, Hycult Biotech, TECO Medical