C3b and factor H: key components of the complement system

Abstract

In all three complement pathways, the central molecule is C3, which, upon activation cleavage, forms the major opsonin C3b – the key component of complement. C3b is also essential for propagation of the complement cascade to the stage of the lytic terminal complement complexes. In order to prevent damage to self cells and tissues and restrict overconsumption of the complement components, C3b molecules need to be controlled by factor H. Defect in C3 functions leads to compromised microbial defence and increased susceptibility to certain autoimmune diseases. Deficiency of factor H, or a functional defect in its N terminus, often leads to membranoproliferative glomerulonephritis and complement depletion, owing to continuous overconsumption of C3. Defect in the factor H C terminus leads to a dramatically increased risk of atypical hemolytic uremic syndrome. In addition, recently, a polymorphism in the middle part of factor H (Y402H) has been shown to be the major risk factor for the most common cause of blindness in the industrialized world: age-related macular degeneration. In future, analysis of patient samples for defects in these key complement components may prove useful in diagnosis of these diseases and new therapeutic targets will certainly be the aim for use in the recently recognized factor H-related diseases.

Keywords::

• age-related macular degeneration
• autoimmunity
• complement
• hemolytic uremic syndrome
• immunodeficiency
• innate immunity

Acknowledgements

The work of TS Jokiranta is supported by the Academy of Finland (#201506, #1110367), the Helsinki University Central Hospital EVO-Funds, the Finnish Cultural Foundation and the Sigrid Juselius Foundation.