Complement and its receptors: new insights into human disease

Annu Rev Immunol. 2014;32:433-59. doi: 10.1146/annurev-immunol-032713-120154. Epub 2014 Jan 29.

Abstract

Although new activation and regulatory mechanisms are still being identified, the basic architecture of the complement system has been known for decades. Two major roles of complement are to control certain bacterial infections and to promote clearance of apoptotic cells. In addition, although inappropriate complement activation has long been proposed to cause tissue damage in human inflammatory and autoimmune diseases, whether this is indeed true has been uncertain. However, recent studies in humans, especially those using newly available biological therapeutics, have now clearly demonstrated the pathophysiologic importance of the complement system in several rare diseases. Beyond these conditions, recent genetic studies have strongly supported an injurious role for complement in a wide array of human inflammatory, degenerative, and autoimmune diseases. This review includes an overview of complement activation, regulatory, and effector mechanisms. It then focuses on new understandings gained from genetic studies, ex vivo analyses, therapeutic trials, and animal models as well as on new research opportunities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Complement Activation / immunology
  • Complement System Proteins / genetics
  • Complement System Proteins / immunology*
  • Complement System Proteins / metabolism*
  • Disease Models, Animal
  • Disease Susceptibility / immunology
  • Genetic Predisposition to Disease
  • Humans
  • Protein Binding
  • Receptors, Complement / metabolism*
  • Signal Transduction

Substances

  • Carrier Proteins
  • Receptors, Complement
  • Complement System Proteins