title: Complement activation patterns in atypical haemolytic uraemic syndrome during acute phase and in remission.
abstract: Atypical haemolytic uraemic syndrome (aHUS) is associated with (genetic) alterations in alternative complement pathway. Nevertheless, comprehensive evidence that the complement system in aHUS patients is more prone to activation is still lacking. Therefore, we performed a thorough analysis of complement activation in acute phase and in remission of this disease. Complement activation patterns of the aHUS patients in acute phase and in remission were compared to those of healthy controls. Background levels of complement activation products C3b/c, C3bBbP and terminal complement complex (TCC) were measured using enzyme-linked immunosorbent assay (ELISA) in ethylenediamine tetraacetic acid (EDTA) plasma. In vitro-triggered complement activation in serum samples was studied using zymosan-coating and pathway-specific assay. Furthermore, efficiencies of the C3b/c, C3bBbP and TCC generation in fluid phase during spontaneous activation were analysed. Patients with acute aHUS showed elevated levels of C3b/c (P < 0·01), C3bBbP (P < 0·0001) and TCC (P < 0·0001) in EDTA plasma, while values of patients in remission were normal, compared to those of healthy controls. Using data from a single aHUS patient with complement factor B mutation we illustrated normalization of complement activation during aHUS recovery. Serum samples from patients in remission showed normal in vitro patterns of complement activation and demonstrated normal kinetics of complement activation in the fluid phase. Our data indicate that while aHUS patients have clearly activated complement in acute phase of the disease, this is not the case in remission of aHUS. This knowledge provides important insight into complement regulation in aHUS and may have an impact on monitoring of these patients, particularly when using complement inhibition therapy.
authors: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: E B
authors: EB
authors: Volokhina
authors: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: D
authors: D
authors: Westra
authors: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: T J A M
authors: TJ
authors: van der Velden
authors: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: N C A J
authors: NC
authors: van de Kar
authors: Department of Immunology, Oslo University Hospital, Oslo, Norway.|K. G. Jebsen IRC, University of Oslo, Oslo, Norway.|Research Laboratory, Nordland Hospital, Bodø, Norway.|Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors: T E
authors: TE
authors: Mollnes
authors: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium.
authors: L P
authors: LP
authors: van den Heuvel
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation / Q000187:drug effects; D003179:Complement C3b / Q000378:metabolism*; D011415:Complement Factor B / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000187:drug effects; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D053657:Platelet-Rich Plasma; D020033:Protein Isoforms / Q000097:blood; D012074:Remission Induction; D006435:Renal Dialysis; D015054:Zymosan / Q000494:pharmacology
chemical_list: D015938:Complement Membrane Attack Complex; D020033:Protein Isoforms; D003179:Complement C3b; D017242:Complement Factor H; D015054:Zymosan; D011415:Complement Factor B
keywords: biomarkers; clinical immunology; complement activation; haemolytic uraemic syndrome