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

Noone D, Al-Matrafi J, Tinckam K, Zipfel PF, Herzenberg AM, Thorner PS, Pluthero FG, Kahr WH, Filler G, Hebert D, Harvey E, Licht C (2012) Antibody mediated rejection associated with complement factor h-related protein 3/1 deficiency successfully treated with eculizumab. Am J Transplant 12(9), 2546-2553.

Abstract

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.

Leibniz-HKI-Authors

Peter F. Zipfel

Identifier

doi: 10.1111/j.1600-6143.2012.04124.x

PMID: 22681773