title: Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome.
abstract: The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS.
  
  
  
  Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, αFH) and genetic profiles (CFH, CFI, CD46, CFB, C3) of the alternative complement pathway were prospectively determined in the acute and convalescent phase of disease in children newly diagnosed with STEC-HUS or aHUS. Serological profiles were compared with those of 90 age-matched controls.
  
  
  
  Thirty-seven patients were studied (26 STEC-HUS, 11 aHUS). In 39 % of them, including 28 % of STEC-HUS patients, we identified a genetic and/or acquired complement abnormality. In all patient groups, the levels of investigated alternative pathway (AP) activation markers were elevated in the acute phase and normalized in remission. The levels were significantly higher in aHUS than in STEC-HUS patients.
  
  
  
  In both infection-induced HUS and aHUS patients, complement is activated in the acute phase of the disease but not during remission. The C3d/C3 ratio displayed the best discrepancy between acute and convalescent phase and between STEC-HUS and aHUS and might therefore be used as a biomarker in disease diagnosis and monitoring. The presence of aberrations in the alternative complement pathway in STEC-HUS patients was remarkable, as well.
authors.affiliation: Department of Pediatric Nephrology (804), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Dineke.Westra@radboudumc.nl.
authors.forename: Dineke
authors.initials: D
authors.lastname: Westra
authors.affiliation: Department of Pediatric Nephrology (804), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Volokhina
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Renate G
authors.initials: RG
authors.lastname: van der Molen
authors.affiliation: Department of Pediatric Nephrology (804), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Thea J A M
authors.initials: TJ
authors.lastname: van der Velden
authors.affiliation: Department of Pediatric Nephrology (804), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Jeronimus-Klaasen
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Joop
authors.initials: J
authors.lastname: Goertz
authors.affiliation: Department of Pediatric Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gracchi
authors.affiliation: Department of Pediatric Nephrology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Eiske M
authors.initials: EM
authors.lastname: Dorresteijn
authors.affiliation: Department of Pediatric Nephrology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Antonia H M
authors.initials: AH
authors.lastname: Bouts
authors.affiliation: Department of Pediatric Nephrology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Mandy G
authors.initials: MG
authors.lastname: Keijzer-Veen
authors.affiliation: Department of Pediatric Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joanna A E
authors.initials: JA
authors.lastname: van Wijk
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Bakker
authors.affiliation: Department of Medical Microbiology and Immunology, Sint Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: Roos
authors.affiliation: Department of Pediatric Nephrology (804), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.|Department of Pediatrics, Department of Growth and Regeneration, University Hospital Leuven, Leuven, Belgium.
authors.forename: Lambert P
authors.initials: LP
authors.lastname: van den Heuvel
authors.affiliation: Department of Pediatric Nephrology (804), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Nicole C A J
authors.initials: NC
authors.lastname: van de Kar
mesh_terms: D000293:Adolescent; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology; D003170:Complement Pathway, Alternative / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D012008:Recurrence; D054323:Shiga-Toxigenic Escherichia coli
chemical_list: D015415:Biomarkers; D017242:Complement Factor H
keywords: Atypical HUS; Children; Complement; Genetic aberrations; Hemolytic uremic syndrome; STEC