title: Of mice and men: The factor H protein family and complement regulation.
abstract: For decades immunological research has relied, with variable success, on mouse models to investigate diseases and possible therapeutic interventions. With the approval of the first therapeutic antibody targeting complement, called eculizumab, as therapy in paroxysmal nocturnal hemoglobinuria (PNH) and more recently atypical hemolytic uremic syndrome (aHUS), the viability of targeting the complement system was demonstrated. The potent, endogenous complement regulators have become of increasing interest as templates for designing and developing new therapeutics. Recently, complement inhibitors based on (parts of) the human complement regulator factor H (FH) are being examined for therapeutic intervention in inflammatory conditions. The first step to evaluate the potency of a new drug is often testing it in a mouse model for the target disease. However, translating results to human conditions requires a good understanding of similarities and, more importantly, differences between the human and mouse complement system and particularly regulation. This review will provide a comprehensive overview of the complement regulator FH and its closely related proteins and current views on their role in mice and men.
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner laboratory of the Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Pediatric Hematology, Immunology & Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, Amsterdam, the Netherlands. Electronic address: r.pouw@sanquin.nl.
authors.forename: R B
authors.initials: RB
authors.lastname: Pouw
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner laboratory of the Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: Vredevoogd
authors.affiliation: Department of Pediatric Hematology, Immunology & Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, Amsterdam, the Netherlands; Department of Blood Cell Research, Sanquin Blood Supply, Division Research and Landsteiner laboratory of the Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: Kuijpers
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner laboratory of the Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Wouters
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000276:immunology*; D003176:Complement C3 / Q000235:genetics / Q000276:immunology; D003182:Complement C5 / Q000235:genetics / Q000276:immunology; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D051379:Mice; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D001798:Blood Proteins; D003176:Complement C3; D003182:Complement C5; C100631:factor H-related protein 1; D017242:Complement Factor H
keywords: Complement; Factor H; Human; Mouse; Regulation