title: Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency.
abstract: Atypical hemolytic uremic syndrome (aHUS) is a severe renal disease that is associated with defective complement regulation caused by multiple factors. We previously described the deficiency of factor H-related proteins CFHR1 and CFHR3 as predisposing factor for aHUS. Here we identify in an extended cohort of 147 aHUS patients that 16 juvenile individuals (ie, 11%) who either lacked the CFHR1/CFHR3 completely (n = 14) or showed extremely low CFHR1/CFHR3 plasma levels (n = 2) are positive for factor H (CFH) autoantibodies. The binding epitopes of all 16 analyzed autoantibodies were localized to the C-terminal recognition region of factor H, which represents a hot spot for aHUS mutations. Thus we define a novel subgroup of aHUS, termed DEAP HUS (deficiency of CFHR proteins and CFH autoantibody positive) that is characterized by a combination of genetic and acquired factors. Screening for both factors is obviously relevant for HUS patients as reduction of CFH autoantibody levels represents a therapeutic option.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
authors.forename: Stefanie
authors.initials: S
authors.lastname: Strobel
authors.forename: Svante L H
authors.initials: SL
authors.lastname: Zipfel
authors.forename: Heiko
authors.initials: H
authors.lastname: Richter
authors.forename: Stefan
authors.initials: S
authors.lastname: Heinen
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003180:Complement C3b Inactivator Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017242:Complement Factor H / Q000276:immunology*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D010375:Pedigree
chemical_list: D001323:Autoantibodies; D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H