title: 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.affiliation: Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Damien
authors.initials: D
authors.lastname: Noone
authors.forename: Aoife
authors.initials: A
authors.lastname: Waters
authors.forename: Fred G
authors.initials: FG
authors.lastname: Pluthero
authors.forename: Denis F
authors.initials: DF
authors.lastname: Geary
authors.forename: Michael
authors.initials: M
authors.lastname: Kirschfink
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology; D002648:Child; D017242:Complement Factor H / Q000172:deficiency / Q000276:immunology; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000188:drug therapy*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D010949:Plasma; D010951:Plasma Exchange; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D017242:Complement Factor H; C481642:eculizumab