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01-05-2014 | Original Article

Successful treatment of DEAP-HUS with eculizumab

Authors: Damien Noone, Aoife Waters, Fred G. Pluthero, Denis F. Geary, Michael Kirschfink, Peter F. Zipfel, Christoph Licht

Published in: Pediatric Nephrology | Issue 5/2014

Abstract

Background

Deficiency of complement factor H-related (CFHR) proteins and CFH autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) represents a unique subgroup of complement-mediated atypical HUS (aHUS). Autoantibodies to the C-terminus of CFH block CFH surface recognition and mimic mutations found in the genetic form of (CFH-mediated) aHUS. CFH autoantibodies are found in 10–15 % of aHUS patients and occur—so far unexplained—almost exclusively in the background of CFHR1 or CFHR3/CFHR1 deletions.

Methods

As a well-defined role for eculizumab in the treatment of complement-mediated aHUS is becoming established, its role in DEAP-HUS is less conspicuous, where a B-cell-depleting and immunosuppressive treatment strategy is being proposed in the literature.

Results

We here show eculizumab to be safe and effective in maintaining a disease-free state, without recurrence, in a previously plasma-therapy-dependent DEAP-HUS patient, and in another patient in whom, although showing a good clinical response to plasma therapy, the therapy was hampered by allergic reactions to fresh frozen plasma and contend there is a rationale for the use of eculizumab in concert with an immunosuppressive strategy in the treatment of DEAP-HUS. Considering the high rate of early relapse, the possible coexistence and contribution of both known and unknown complement-gene mutations, the probable pathogenic role of CFHR1 as a complement alternative pathway (CAP) regulator, the experimental nature of measuring and using anti-CFH autoantibodies to guide management, and until the positive reports of immunosuppression in addition to plasma therapy are confirmed in prospective studies, we feel that a complement-directed therapy should not be neglected in DEAP-HUS. Serial CFH autoantibody titer testing may become a valuable tool to monitor treatment response, and weaning patients off eculizumab may become an option once CFH autoantibody levels are depleted.

Conclusions

A prospective study of eculizumab treatment in a larger cohort of DEAP-HUS patients is required to validate the applicability of our positive experience.

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Title: Successful treatment of DEAP-HUS with eculizumab
Authors: Damien Noone
Aoife Waters
Fred G. Pluthero
Denis F. Geary
Michael Kirschfink
Peter F. Zipfel
Christoph Licht
Publication date: 01-05-2014
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 5/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-013-2654-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Successful treatment of DEAP-HUS with eculizumab

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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