title: Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome.
abstract: OBJECTIVE
  This study evaluated the relevance of complement factor H (CFH)-related protein (CFHR) 1 deficiency in pediatric patients with atypical hemolytic uremic syndrome (aHUS) by evaluating both the frequency of deletions in CFHR1 and the presence of complement factor H (CFH) antibodies.
  
  
  METHODS
  A total of 116 patients (mainly from central Europe) and 118 healthy blood donors were included from 2001 to 2012. The presence of CFHR1 gene deletions was determined in 90 pediatric patients with aHUS and 118 controls by an easy, fast, and cheap PCR assay; 100 patients with aHUS and 42 controls were tested for CFH antibodies by ELISA. Questionnaires were administered to evaluate the clinical and laboratory data.
  
  
  RESULTS
  Homozygous deletion in CFHR1 was detected in 32% of the patients with aHUS tested, compared with 2.5% of controls (P<0.001). CFH antibodies were present in 25% of the patients and none of the controls. CFH antibodies were detected in 82% of patients with homozygous CFHR1 gene deletion and in 6% of patients without. CFH antibody-positive patients with aHUS showed a significantly lower platelet nadir at disease onset and significantly less frequent involvement of the central nervous system than did antibody-negative patients. Antibody-positive patients also received plasma therapy more often.
  
  
  CONCLUSIONS
  Homozygous deletion in CFHR1 is strongly associated with occurrence of CFH antibodies in pediatric patients with aHUS. However, despite this apparent genetic disease predisposition, it cannot be considered an exclusive cause for aHUS. Initial presentation of Shiga toxin-negative HUS with severe thrombocytopenia and no central nervous system complications in pediatric patients is especially suspicious for CFH antibody aHUS.
authors.affiliation: Department of Pediatrics I, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hofer
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Janecke
authors.forename: L B
authors.initials: LB
authors.lastname: Zimmerhackl
authors.forename: Magdalena
authors.initials: M
authors.lastname: Riedl
authors.forename: Alejandra
authors.initials: A
authors.lastname: Rosales
authors.forename: Thomas
authors.initials: T
authors.lastname: Giner
authors.forename: Gerard
authors.initials: G
authors.lastname: Cortina
authors.forename: Carola J
authors.initials: CJ
authors.lastname: Haindl
authors.forename: Barbara
authors.initials: B
authors.lastname: Petzelberger
authors.forename: Miriam
authors.initials: M
authors.lastname: Pawlik
authors.forename: Verena
authors.initials: V
authors.lastname: Jeller
authors.forename: Udo
authors.initials: U
authors.lastname: Vester
authors.forename: Bettina
authors.initials: B
authors.lastname: Gadner
authors.forename: Michael
authors.initials: M
authors.lastname: van Husen
authors.forename: Michael L
authors.initials: ML
authors.lastname: Moritz
authors.forename: Reinhard
authors.initials: R
authors.lastname: Würzner
authors.forename: Therese
authors.initials: T
authors.lastname: Jungraithmayr
mesh_terms: D000367:Age Factors; D065766:Atypical Hemolytic Uremic Syndrome; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D003180:Complement C3b Inactivator Proteins / Q000172:deficiency* / Q000235:genetics*; D017242:Complement Factor H / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D001323:Autoantibodies; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H