title: Factor H-related proteins determine complement-activating surfaces.
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.
authors.affiliation: MTA-ELTE 'Lendület' Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain; Centro de Investigación Biomédica en Enfermedades Raras, Madrid, Spain.
authors.forename: Agustin
authors.initials: A
authors.lastname: Tortajada
authors.affiliation: MTA-ELTE Immunology Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Barbara
authors.initials: B
authors.lastname: Uzonyi
authors.affiliation: Centre for Complement and Inflammation Research (CCIR), Department of Medicine, Imperial College, London, UK; Inmunología, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain; Hospital 12 de Octubre Institute of Health Research, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Goicoechea de Jorge
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain; Centro de Investigación Biomédica en Enfermedades Raras, Madrid, Spain. Electronic address: srdecordoba@cib.csic.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez de Córdoba
mesh_terms: D001053:Apolipoproteins / Q000235:genetics / Q000276:immunology*; D001798:Blood Proteins / Q000235:genetics / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins / Q000235:genetics / Q000276:immunology*; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D018448:Models, Immunological
chemical_list: D001053:Apolipoproteins; D001798:Blood Proteins; C517621:CFHR1 protein, human; C586681:CFHR2 protein, human; C105970:CFHR3 protein, human; C105092:CFHR4 protein, human; C432223:CFHR5 protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H; D003165:Complement System Proteins
keywords: CFHRs; complement; disease susceptibility; factor H; factor H-related proteins