Antibody mediated rejection associated with complement factor h-related protein 3/1 deficiency successfully treated with eculizumab

Am J Transplant. 2012 Sep;12(9):2546-53. doi: 10.1111/j.1600-6143.2012.04124.x. Epub 2012 Jun 8.


Antibody mediated rejection (AMR) activates the classical complement pathway and can be detrimental to graft survival. AMR can be accompanied by thrombotic microangiopathy (TMA). Eculizumab, a monoclonal C5 antibody prevents induction of the terminal complement cascade (TCC) and has recently emerged as a therapeutic option for AMR. We present a highly sensitized 13-year-old female with end-stage kidney disease secondary to spina bifida-associated reflux nephropathy, who developed severe steroid-, ATG- and plasmapheresis-resistant AMR with TMA 1 week post second kidney transplant despite previous desensitization therapy with immunoglobulin infusions. Eculizumab rescue therapy resulted in a dramatic improvement in biochemical (C3; creatinine) and hematological (platelets) parameters within 6 days. The patient was proven to be deficient in complement Factor H-related protein 3/1 (CFHR3/1), a plasma protein that regulates the complement cascade at the level of C5 conversion and has been involved in the pathogenesis of atypical hemolytic uremic syndrome caused by CFH autoantibodies (DEAP-HUS). CFHR1 deficiency may have worsened the severe clinical progression of AMR and possibly contributed to the development of donor-specific antibodies. Thus, screening for CFHR3/1 deficiency should be considered in patients with severe AMR associated with TMA.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antibodies / immunology*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Blood Proteins / immunology*
  • Complement C3b Inactivator Proteins / immunology*
  • Female
  • Graft Rejection / drug therapy*
  • Graft Rejection / immunology*
  • Humans


  • Antibodies
  • Antibodies, Monoclonal, Humanized
  • Blood Proteins
  • CFHR1 protein, human
  • CFHR3 protein, human
  • Complement C3b Inactivator Proteins
  • eculizumab