Antibody mediated rejection associated with complement factor h-related protein 3/1 deficiency successfully treated with eculizumab.
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.
Division of Nephrology, The Hospital for Sick Children, University of Toronto, ON, Canada.
D
D
Noone
J
J
Al-Matrafi
K
K
Tinckam
P F
PF
Zipfel
A M
AM
Herzenberg
P S
PS
Thorner
F G
FG
Pluthero
W H A
WH
Kahr
G
G
Filler
D
D
Hebert
E
E
Harvey
C
C
Licht
D000293:Adolescent; D000906:Antibodies / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001798:Blood Proteins / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans
D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; C481642:eculizumab