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Successful discontinuation of eculizumab under immunosuppressive therapy in DEAP-HUS

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Abstract

Background

Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome (DEAP-HUS), which is characterized by the deficiency of complement-factor H-related (CFHR) plasma proteins and the subsequent formation of autoantibodies against complement factor H (CFH), has been reported to have an adverse outcome in one third of patients. Therapy options include prompt removal of antibodies by plasma exchange and immunosuppressive therapy. Recently, restoration of complement control using the monoclonal antibody eculizumab has been shown to be effective as first- and as second-line therapy in cases of therapy resistance or severe side effects of the applied therapy.

Diagnosis/treatment

Here, we report a 6-year-old girl with DEAP-HUS and first-line therapy with eculizumab under immunosuppressive therapy with glucocorticoids and mycophenolate mofetil (MMF). This therapy led to a prompt and sustained clinical recovery, to a stable reduction of complement activation, and to a rapid decline in autoantibody titer. A second increase in the autoantibody titer was successfully treated with methylprednisolone and the child remained in remission. After 8.3 months of sustained complement control and 4.5 months of stable antibody suppression, eculizumab was successfully discontinued without any sign of relapse.

Conclusions

To our knowledge, this is the first reported case of a child with DEAP-HUS treated with the combination of eculizumab and immunosuppression as first-line therapy avoiding any HUS- or therapy-related complications and resulting in prompt clinical recovery. Importantly, clinical remission is maintained after discontinuation of eculizumab under stable immunosuppression.

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Abbreviations

ADAMTS13:

A disintegrin and metalloproteinase with thrombospondin-1 motifs (13th member of the family)

aHUS:

Atypical hemolytic uremic syndrome

ANAs:

Anti-nuclear antibodies

ANCAs:

Anti-neutrophil cytoplasmic antibodies

AUC:

Area under the curve

BSA:

Body surface area

CFH/CFI/CFB:

Complement factor H/I/B

CFHR:

Complement factor H-related

CKD:

Chronic kidney disease

DEAP-HUS:

Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome

DGKE:

Diacylglycerol kinase epsilon

IS:

Immunosuppression

LDH:

Lactate dehydrogenase

MMACHC:

Methylmalonic aciduria and homocystinuria type C protein

MMF:

Mycophenolate mofetil

MPA:

Mycophenolic acid

PI:

Plasma infusions

RRT:

Renal replacement therapy

sC5b-9:

Soluble C5b-9

THBD:

Thrombomodulin

TPE:

Therapeutic plasma exchange

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Authors and Affiliations

  1. Pediatric Nephrology, Children’s and Adolescents’ Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany

    Agnes Hackl, Rasmus Ehren, Lutz T. Weber & Sandra Habbig

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

    Michael Kirschfink

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

    Peter F. Zipfel

  4. Friedrich Schiller University, Jena, Germany

    Peter F. Zipfel

  5. Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany

    Bodo B. Beck

  6. Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany

    Bodo B. Beck

Authors
  1. Agnes Hackl
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  2. Rasmus Ehren
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  3. Michael Kirschfink
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  4. Peter F. Zipfel
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  5. Bodo B. Beck
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  6. Lutz T. Weber
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  7. Sandra Habbig
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Corresponding author

Correspondence to Sandra Habbig.

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There was no financial support or funding for this study

Conflicts of interest

AH and BBB received fees for invited lectures from Alexion. MK received fees for invited lectures and advisory board meetings from Alexion and for lectures from Euro Diagnostica. PFZ received lecture fees from Alexion. LTW is a member of the Scientific Advisory Board of Alexion. RE and SH declare that they have no conflicts of interest.

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Hackl, A., Ehren, R., Kirschfink, M. et al. Successful discontinuation of eculizumab under immunosuppressive therapy in DEAP-HUS. Pediatr Nephrol 32, 1081–1087 (2017). https://doi.org/10.1007/s00467-017-3612-9

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  • DOI: https://doi.org/10.1007/s00467-017-3612-9

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