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Successful treatment of DEAP-HUS with eculizumab

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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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Acknowledgments

DN, AW, FGP, DFG, MK: none

PFZ received speaking honoraria form Alexion Pharmaceuticals, Inc.

CL has a financial relationship with Alexion Pharmaceuticals, Inc. via consultancy, paid speaking, and unrestricted research grants

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Authors and Affiliations

  1. Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Damien Noone, Aoife Waters, Denis F. Geary & Christoph Licht

  2. Institute for Immunology, University of Heidelberg, Heidelberg, Germany

    Michael Kirschfink

  3. Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany

    Peter F. Zipfel

  4. Friedrich-Schiller University, Jena, Germany

    Peter F. Zipfel

  5. Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada

    Fred G. Pluthero & Christoph Licht

  6. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Denis F. Geary & Christoph Licht

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  1. Damien Noone
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  2. Aoife Waters
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  3. Fred G. Pluthero
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  6. Peter F. Zipfel
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Correspondence to Christoph Licht.

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Noone, D., Waters, A., Pluthero, F.G. et al. Successful treatment of DEAP-HUS with eculizumab. Pediatr Nephrol 29, 841–851 (2014). https://doi.org/10.1007/s00467-013-2654-x

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  • DOI: https://doi.org/10.1007/s00467-013-2654-x

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