Effect of a proteasome inhibitor plus steroids on HLA antibodies in sensitized patients awaiting a renal transplant.
BACKGROUND
This prospective monocentric study investigated the effect of corticosteroids plus bortezomib to reduce anti-HLA antibodies before renal transplantation.


METHODS
Included were 23 patients with stable immunization against HLA and awaiting a kidney transplant (KT). Treatment consisted of bortezomib (1.3 mg/m) plus 40 mg of dexamethasone intravenously on days 1, 3, 8, and 10 (B+S). Class I and II anti-HLAs were determined using the single-antigen beads assay at day 0 (D0), month 1 (M1), M3, and M6.


RESULTS
Antibodies against 96 class I and 76 class II antigens were investigated and patients had a mean number of 49 (± 21) antibodies against HLA on D0: 31 were against HLA class I and 17 were against HLA class II. At D0, the median was 10,734 (range, 1096-18,513) for the highest mean fluorescent intensity (hAb) anti-class I antibodies and 11,189 (range, 1276-19,176) for class II. By M3, 41% of patients had a greater than 25% decrease in class 1 hAbs and 60% by M6. By M3, 33% of patients had a greater than 25% decrease in class II hAbs and 42% by M6. At M6, 54% of anti-HLA antibodies had a sustained decrease by more than 25% and 36% were decreased by more than 50%. No predictive factors for decreased antibodies after bortezomib plus steroid therapy were identified. No serious adverse event was observed. Thereafter, 11 of 23 patients received successful transplants without having experienced acute rejection (follow-up, 18 months).


CONCLUSIONS
B+S is an effective alternative therapy for reducing class I and II anti-HLA, regardless of other previous treatments.
1 Service de néphrologie, Hôpital Le Kremlin Bicêtre, APHP, IFRNT, Université Paris sud, Paris, France. 2 Laboratoire d'histocompatibilité Hôpital Saint Louis APHP, Paris, France. 3 CHU-hôpitaux de Rouen, Rouen, France. 4 INSERM UMR1014, Hopital P Brousse, Villejuif, Paris, France. 5 Address correspondence to: Prof. Antoine Durrbach, Service de Néphrologie, Hôpital Kremlin Bicêtre, Université Paris sud, Paris, France.
Olivier
O
Aubert
Caroline
C
Suberbielle
Rémi
R
Gauthe
Helene
H
Francois
Erika Nnang
EN
Obada
Antoine
A
Durrbach
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D057234:Preoperative Period; D011446:Prospective Studies; D061988:Proteasome Inhibitors / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage; D051437:Renal Insufficiency / Q000628:therapy*; D013256:Steroids / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D000906:Antibodies; D001897:Boronic Acids; D006680:HLA Antigens; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013256:Steroids; D000069286:Bortezomib; D003907:Dexamethasone