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Clin Immunol. 2015 Oct;160(2):237-43. doi: 10.1016/j.clim.2015.05.018. Epub 2015 Jun 23.

Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome.

Author information

  • 1Department of Pediatric Nephrology (774), Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands.
  • 2Research Laboratory, Nordland Hospital, P. O. Box 1480, 8092 Bodø, Norway.
  • 3Department of Nephrology (464), Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • 4Department of Pediatric Nephrology (774), Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Laboratory Medicine (774), Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Pediatrics, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
  • 5Research Laboratory, Nordland Hospital, P. O. Box 1480, 8092 Bodø, Norway; Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, P. O. Box 6050 Langnes, 9037 Tromsø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway; Department of Immunology, Oslo University Hospital, and K.G Jebsen IRC, University of Oslo, P.B. 4950 Nydalen, NO-0424 Oslo, Norway. Electronic address: t.e.mollnes@medisin.uio.no.

Abstract

Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow-up. We documented that the Wieslab® complement screen assay showed a sensitivity of 1-2% of C5 activity by adding purified C5 or normal human serum to a C5 deficient serum. All the patient samples obtained during the treatment course, were completely blocked for terminal complement pathway activity for up to four weeks after the eculizumab infusion. Levels of complexes between eculizumab and C5 were inversely correlated to the complement activity (p=0.01). Moreover, titrating serum from eculizumab-treated patients into normal serum revealed that eculizumab was present in excess up to four weeks after infusion. Thus, we demonstrate sensitive, reliable and easy-performed assays which can be used to design individual eculizumab dosage regimens.

Copyright © 2015. Published by Elsevier Inc.

KEYWORDS:

Complement; Eculizumab; Hemolytic uremic syndrome; Personalized therapy

PMID:
26111482
[PubMed - indexed for MEDLINE]
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