Successful treatment of DEAP-HUS with eculizumab.

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.

• Authors: Damien Noone, Aoife Waters, Fred G Pluthero, Denis F Geary, Michael Kirschfink, Peter F Zipfel, Christoph Licht
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 29 Issue 5 Pg. 841-51 (May 2014) ISSN: 1432-198X [Electronic] Germany
• PMID: 24249282 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Autoantibodies
• Complement Factor H
• eculizumab

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• Autoantibodies (immunology)
• Child
• Complement Factor H (deficiency, immunology)
• Female
• Hemolytic-Uremic Syndrome (drug therapy)
• Humans
• Kidney Function Tests
• Male
• Plasma
• Plasma Exchange
• Treatment Outcome