Document Detail

Monitoring and modeling treatment of atypical hemolytic uremic syndrome.
MedLine Citation:
PMID:  23220071     Owner:  NLM     Status:  MEDLINE    
Atypical hemolytic uremic syndrome (aHUS), is mainly present in children, who have high risks of end-stage kidney disease (ESKD), post-transplant recurrence and death. aHUS is linked to defective regulation of the complement alternative pathway (AP), with a prominent cause being mutation/inhibition of the negative regulator complement factor H (CFH). CFH function can be restored via infusion of fresh frozen plasma (FFP), a treatment that was effective for several years in a patient heterozygous for a cfh mutation, before the patient progressed to ESKD. While on dialysis, FFP was replaced with eculizumab, which blocks C5 cleavage and thus halts progression of the terminal complement pathway. Patient plasma samples collected during FFP and eculizumab treatment phases were assessed for AP activity (via erythrocyte lysis assays) and for overall complement activity (via ELISA-based screen). Assay results indicated that FFP partially restored AP regulation, an observation supported by in vitro modeling of FFP treatment using purified CFH, while eculizumab completely blocked complement activity. The same approach was used to model in vitro a potential aHUS treatment approach based on blocking the AP effector properdin (complement factor P; CFP) with an anti-properdin antibody. These results provide insights into the efficacy of aHUS treatment and highlight the usefulness of in vitro assays in monitoring and predicting therapeutic responses and testing new treatment possibilities.
Stefan Heinen; Fred G Pluthero; Viola F van Eimeren; Susan E Quaggin; Christoph Licht
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-03
Journal Detail:
Title:  Molecular immunology     Volume:  54     ISSN:  1872-9142     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-03-21     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  84-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Antibodies, Monoclonal, Humanized / therapeutic use
Blood Transfusion / adverse effects
Decision Support Techniques*
Hemolytic-Uremic Syndrome / complications,  therapy*
Kidney Failure, Chronic / etiology,  prevention & control,  therapy
Monitoring, Physiologic / methods*
Renal Dialysis
Treatment Outcome
Reg. No./Substance:
0/Antibodies, Monoclonal, Humanized; A3ULP0F556/eculizumab

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