title: The role of heparan sulfate as determining pathogenic factor in complement factor H-associated diseases.
abstract: Complement factor H (FH) systemically inhibits excessive complement activation in the microenvironment of host cells, but for instance not on microbes. This self-recognition is mediated by two binding sites that recognize distinctly sulfated heparan sulfate (HS) domains. The interaction with HS not only concentrates FH on host cells, but directly affects its activity, evoking novel models of conformational activation. Genetic aberrations in the HS-binding domains systemically disturb the protective function of FH, yet the resulting loss of complement control affects mainly ocular and renal tissues. Recent results suggest that the specific expression of HS domains in these tissues restricts the interaction of HS to a single binding site within FH. This lack of redundancy could predispose eyes and kidneys to complement-mediated damage, making HS a central determinant for FH-associated diseases.
authors.affiliation: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Electronic address: Markus.Loeven@radboudumc.nl.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Loeven
authors.affiliation: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Electronic address: Angelique.Meulemans-Rops@radboudumc.nl.
authors.forename: Angelique L W M M
authors.initials: AL
authors.lastname: Rops
authors.affiliation: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Electronic address: Jo.Berden@radboudumc.nl.
authors.forename: Jo H M
authors.initials: JH
authors.lastname: Berden
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 ZA, Leiden, The Netherlands. Electronic address: M.R.Daha@lumc.nl.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 ZA, Leiden, The Netherlands. Electronic address: A.J.Rabelink@lumc.nl.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Electronic address: Johan.vanderVlag@radboudumc.nl.
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
mesh_terms: D017242:Complement Factor H / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology*; D009928:Organ Specificity
chemical_list: D017242:Complement Factor H; D006497:Heparan Sulfate
keywords: Age-related macular degeneration; Complement factor H; Complement-mediated nephropathies; Endothelial microenvironment; Glycocalyx; Heparan sulfate