The Factor H protein family: The switchers of the complement alternative pathway

Immunol Rev. 2023 Jan;313(1):25-45. doi: 10.1111/imr.13166. Epub 2022 Nov 16.

Abstract

The factor H (FH) protein family is emerging as a complex network of proteins controlling the fate of the complement alternative pathway (AP) and dictating susceptibility to a wide range of diseases including infectious, inflammatory, autoimmune, and degenerative diseases and cancer. Composed, in man, of seven highly related proteins, FH, factor H-like 1, and 5 factor H-related proteins, some of the FH family proteins are devoted to down-regulating the AP, while others exert an opposite function by promoting AP activation. Recent findings have provided insights into the molecular mechanisms defining their biological roles and their pathogenicity, illustrating the relevance that the balance between the regulators and the activators within this protein family has in defining the outcome of complement activation on cell surfaces. In this review we will discuss the emerging roles of the factor H protein family, their impact in the complement cascade, and their involvement in the pathogenesis of complement-mediated diseases associated with the AP dysregulation.

Keywords: FHL-1; FHRs; Factor H; alternative pathway; complement.

Publication types

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

MeSH terms

  • Complement Activation
  • Complement Factor H* / metabolism
  • Complement Pathway, Alternative
  • Complement System Proteins* / metabolism
  • Humans

Substances

  • Complement Factor H
  • Complement System Proteins