Factor H-related Proteins Determine Complement-Activating Surfaces

Trends Immunol. 2015 Jun;36(6):374-84. doi: 10.1016/j.it.2015.04.008. Epub 2015 May 13.

Abstract

Complement factor H-related proteins (FHRs) are strongly associated with different diseases involving complement dysregulation, which suggests a major role for these proteins regulating complement activation. Because FHRs are evolutionarily and structurally related to complement inhibitor factor H (FH), the initial assumption was that the FHRs are also negative complement regulators. Whereas weak complement inhibiting activities were originally reported for these molecules, recent developments indicate that FHRs may enhance complement activation, with important implications for the role of these proteins in health and disease. We review these findings here, and propose that FHRs represent a complex set of surface recognition molecules that, by competing with FH, provide improved discrimination of self and non-self surfaces and play a central role in determining appropriate activation of the complement pathway.

Keywords: CFHRs; complement; disease susceptibility; factor H; factor H-related proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apolipoproteins / genetics
  • Apolipoproteins / immunology*
  • Blood Proteins / genetics
  • Blood Proteins / immunology*
  • Complement Activation / immunology*
  • Complement C3b Inactivator Proteins / genetics
  • Complement C3b Inactivator Proteins / immunology*
  • Complement Factor H / genetics
  • Complement Factor H / immunology
  • Complement System Proteins / genetics
  • Complement System Proteins / immunology*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Models, Immunological

Substances

  • Apolipoproteins
  • Blood Proteins
  • CFHR1 protein, human
  • CFHR2 protein, human
  • CFHR3 protein, human
  • CFHR4 protein, human
  • Complement C3b Inactivator Proteins
  • FHR5 protein, human
  • Complement Factor H
  • Complement System Proteins