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Complement, roles in renal disease and modulation for therapy

Hepburn, Natalie Jayne, Ruseva, Marieta Milkova, Harris, Claire Louise and Morgan, Bryan Paul 2008. Complement, roles in renal disease and modulation for therapy. Clinical Nephrology 70 (5) , pp. 357-376.

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Abstract

The complement system, an essential part of the innate immune system, defends the host against invading pathogens, prevents immune complex disease and aids the acquired immune response. Under normal conditions the host is protected from complement attack by an array of complement regulatory proteins. However, in certain contexts inappropriate complement activation can occur associating the C system with a variety of disease pathologies. This review focuses upon the role complement plays in a number of renal pathologies as well as the role of complement in three examples of extrarenal diseases: paroxysmal nocturnal hemoglobinuria, age-related macular degeneration and liver fibrosis. From the evidence discussed it is clear that mutations or polymorphisms in the complement regulators resulting in reduced levels or inefficient action dramatically enhance susceptibility to certain diseases and in particular render the kidney more vulnerable to complement attack. Additionally, deficiency in the complement components can predispose to disease through reduced clearance of apoptotic cells and subsequent generation of complement activating autoantibodies or enhanced formation of convertases resulting in heightened complement activation. As complement has devastating effects, in such disease contexts it has become a therapeutic target. Therapeutic intervention strategies discussed here focus upon the use of recombinant agents, the most promising of which are the anti-C5 antibody-derived reagents. These agents have proved effective in the treatment of paroxysmal nocturnal hemoglobinuria, nephritis and ischemia-reperfusion injuries and will no doubt, along with other reagents currently being developed, prove invaluable in the treatment of renal pathologies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Biosciences
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RB Pathology
Publisher: Dustri-Verlag
ISSN: 0301-0430
Last Modified: 06 Jan 2018 20:19
URI: http://orca.cf.ac.uk/id/eprint/17678

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