title: Atypical hemolytic uremic syndrome associated with complement factor H autoantibodies and CFHR1/CFHR3 deficiency.
abstract: Although genetic defect of complement factor H (CFH) is a common cause of atypical hemolytic uremic syndrome (aHUS), development of autoantibodies to CFH (CFH-Ab) is also known to be an acquired cause of aHUS. Recently, a correlation between the development of CFH-Ab and the deficiency of the CFH-related proteins, CFHR1 and CFHR3, was identified. In this study, plasma complement profiles were measured and genetic analysis of the CFH, CFI, MCP, CFHR1, and CFHR3 genes were performed in three female patients diagnosed with aHUS with positive CFH-Ab. Acute stage plasmas of all the three patients revealed low C3, low or low-normal CFH antigenic levels, and high titers of CFH-Ab. All the patients also showed complete plasma CFHR1 deficiency and homozygous genomic deletion of CFHR1/CFHR3, but none had CFH, CFI, or MCP mutations. All the patients were treated with plasmapheresis, and two patients required additional immunosuppressive therapy. These patients had a novel subgroup of aHUS characterized by a combination of genetic (a homozygous deletion of CFHR1/CFHR3) and acquired (development of CFH-Ab) factors. Patients with this disease may need intensive immunosuppressive therapy in addition to plasmapheresis. Screening for CFH-Ab and the CFHR1/CFHR3 deficiency should be included in the diagnostic tests for patients with aHUS.
authors.affiliation: Department of Pediatrics, Kidney Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Beom Hee
authors.initials: BH
authors.lastname: Lee
authors.forename: Soo Heon
authors.initials: SH
authors.lastname: Kwak
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Shin
authors.forename: So Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Hee Gyung
authors.initials: HG
authors.lastname: Kang
authors.forename: Il Soo
authors.initials: IS
authors.lastname: Ha
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Lee
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: Yong
authors.initials: Y
authors.lastname: Choi
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001798:Blood Proteins / Q000172:deficiency* / Q000235:genetics; D002648:Child; D003180:Complement C3b Inactivator Proteins / Q000172:deficiency* / Q000235:genetics; D017242:Complement Factor H / Q000276:immunology*; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000276:immunology; D006801:Humans
chemical_list: D001323:Autoantibodies; D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H; D003165:Complement System Proteins