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Pediatric Nephrology
Published in: Pediatric Nephrology 8/2019

Open Access 01-08-2019 | Educational Review

The role of properdin in complement-mediated renal diseases: a new player in complement-inhibiting therapy?

Authors: Marloes A. H. M. Michels, Elena B. Volokhina, Nicole C. A. J. van de Kar, Lambertus P. W. J. van den Heuvel

Published in: Pediatric Nephrology | Issue 8/2019

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Abstract

Properdin is known as the only positive regulator of the complement system. Properdin promotes the activity of this defense system by stabilizing its key enzymatic complexes: the complement alternative pathway (AP) convertases. Besides, some studies have indicated a role for properdin as an initiator of complement activity. Though the AP is a powerful activation route of the complement system, it is also involved in a wide variety of autoimmune and inflammatory diseases, many of which affect the kidneys. The role of properdin in regulating complement in health and disease has not received as much appraisal as the many negative AP regulators, such as factor H. Historically, properdin deficiency has been strongly associated with an increased risk for meningococcal disease. Yet only recently had studies begun to link properdin to other complement-related diseases, including renal diseases. In the light of the upcoming complement-inhibiting therapies, it is interesting whether properdin can be a therapeutic target to attenuate AP-mediated injury. A full understanding of the basic concepts of properdin biology is therefore needed. Here, we first provide an overview of the function of properdin in health and disease. Then, we explore its potential as a therapeutic target for the AP-associated renal diseases C3 glomerulopathy, atypical hemolytic uremic syndrome, and proteinuria-induced tubulointerstitial injury. Considering current knowledge, properdin-inhibiting therapy seems promising in certain cases. However, knowing the complexity of properdin’s role in renal pathologies in vivo, further research is required to clarify the exact potential of properdin-targeted therapy in complement-mediated renal diseases.
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Metadata
Title
The role of properdin in complement-mediated renal diseases: a new player in complement-inhibiting therapy?
Authors
Marloes A. H. M. Michels
Elena B. Volokhina
Nicole C. A. J. van de Kar
Lambertus P. W. J. van den Heuvel
Publication date
01-08-2019
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 8/2019
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-018-4042-z

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