Report of the inefficacy of eculizumab in two cases of severe antibody-mediated rejection of renal grafts.
BACKGROUND
Acute antibody-mediated rejection (AMR) is responsible for up to 20% to 30% of acute rejection after kidney transplantation. New therapeutic agents have recently emerged, such as eculizumab, an anticomplement protein-C5 monoclonal antibody. In the setting of renal transplantation, eculizumab has so far proved effective both for preventive and curative treatments of AMR in sensitized patients and patients diagnosed with severe AMR. Unsuccessful eculizumab treatment has only been reported once in the literature by Stegall et al. (Am J Transplant 2011; 11: 2405).


RESULTS
We present two cases of AMR resistant to eculizumab after renal transplantation. One patient received the anti-C5 antibody curatively, and the other patient developed AMR while being treated with eculizumab after a relapse of atypical hemolytic uremic syndrome. The peculiarity of these two cases was the absence of C4d deposition in peritubular capillaries as well as the absence of C1q-binding donor-specific anti-human leukocyte antigen alloantibody, as determined retrospectively, suggesting that a complement-independent mechanism underlies the pathogenesis of these AMR.


CONCLUSIONS
The use of eculizumab in C4d-negative or C1q-negative AMR does not seem effective.
1 AP-HP, Hôpital Tenon, Urgences Néphrologiques et Transplantation Rénale, Paris, France. 2 AP-HP, Hôpital Saint Louis, Laboratoire d'Histocompatibilité, Paris, France. 3 AP-HP, Hôpital Tenon, Anatomo-pathologie, Paris, France. 4 Sorbonne Universités, UPMC Université Paris, Paris, France. 5 AP-HP, Hôpital Tenon, Hôpital de Jour, Paris, France. 6 Address correspondence to: Alexandre Hertig, M.D., Ph.D., Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, 4 rue de la Chine, 75020, Paris, France.
Maren
M
Burbach
Caroline
C
Suberbielle
Isabelle
I
Brochériou
Christophe
C
Ridel
Laurent
L
Mesnard
Karine
K
Dahan
Eric
E
Rondeau
Alexandre
A
Hertig
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000601:surgery; D015922:Complement C1q / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D003182:Complement C5 / Q000037:antagonists & inhibitors; D051056:Complement Inactivating Agents / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007518:Isoantibodies / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D014019:Tissue Donors; D017211:Treatment Failure
D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D051056:Complement Inactivating Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D015922:Complement C1q; D015935:Complement C4b; C032261:complement C4d; C481642:eculizumab