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Defective Complement Action and Control Defines Disease Pathology for Retinal and Renal Disorders and Provides a Basis for New Therapeutic Approaches

  • Peter F. ZipfelEmail author
  • Nadine Lauer
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 735)

Abstract

The complement system is a central homeostatic system of the vertebrate organism and part of innate immunity. When activated, complement has multiple functions and drives homeostasis and the elimination of infectious microbes (Walport MJ (2001) N Engl J Med 344:1140–1144; Zipfel PF, Skerka C (2009) Nat Rev Immunol 9:729–740). Several inflammatory disorders are caused by defective complement action, and the growing, detailed understanding of the underlying pathophysiological principles translate into therapy with complement inhibitors. As complement inhibitors have been approved for treatment of the complement-mediated disorders hemolytic uremic syndrome (HUS) and paroxysmal nocturnal hemoglobinuria (PNH), there is a growing interest to extended and improve the options for other complement-mediated diseases. Here, we summarize the current understanding and concepts how defective complement action at biological surfaces lead to pathology and disease, and how this understanding can be used for the development of surface targeting complement inhibitors.

Keywords

Retinal Pigment Epithelial Cell Hemolytic Uremic Syndrome Paroxysmal Nocturnal Hemoglobinuria Complement Cascade Terminal Complement Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

aHUS

Atypical hemolytic uremic syndrome

AMD

Age-related macular degeneration

AP

The alternative pathway

CFHR

Complement Factor H-related protein

CP

The classical pathway

CRP

C-reactive protein

DAMPs

Damage-associated molecular patterns

DEAP-HUS

Deficient for CFHR proteins and Factor H autoantibody positive HUS

FHL1

Factor H-like protein

LP

The lectin pathway

mCRP

Monomeric CRP

MDA

Malondialdehyde

MPGN II

Membranoproliferative glomerulonephritis type II

PNH

Paroxysmal nocturnal hemoglobinuria

pCRP

Pentameric CRP

RPE

Retinal pigment epithelial cells

SCR

Short consensus repeat

TCC

Terminal complement complex

Notes

Acknowledgment

The work of the authors is supported by the Deutsche Forschungsgemeinschaft (DFG), and NL is supported by a Ph.D. research grant from the German ProRetina Foundation.

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Infection BiologyLeibniz Institute for Natural Product Research and Infection BiologyJenaGermany
  2. 2.Friedrich Schiller UniversityJenaGermany

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