Protective immunity remains intact after antibody removal by means of proteasome inhibition.
BACKGROUND
Proteasome inhibition abrogates donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) in patients posttransplant. However, its effects on protective humoral immunity to vaccine antigens remain unknown. Herein, we report on bortezomib's safety regarding protective immunity in patients who have experienced HLA antibody reduction/removal.


METHODS
Thirteen living donor renal transplant patients were treated with bortezomib one to two cycles (1.3 mg/m² × 4 doses) and plasmapheresis in 2008 to remove HLA antibodies posttransplant. Serial measurements of HLA antibody were conducted weekly before, during, and after treatment by means of single antigen bead on Luminex (One Lambda Inc., Canoga Park, CA). Measles and tetanus toxoid IgGs were measured quantitatively by using ELISA (American Research Products Inc., Belmont, MA).


RESULTS
All patients treated with bortezomib/plasmapheresis resulted in a primary DSA reduction of more than 50%. In 10 of 13 patients, complete DSA removal (to below 1000 mean fluorescent intensity) occurred. At 1 year posttreatment, antibody intensity remains significantly depressed in the group as a whole. Despite the significant effect on antibody production, tetanus toxoid and measles IgG levels remained unchanged and above the level of protection at 1 year posttreatment.


CONCLUSIONS
These data indicate that proteasome inhibitors plus plasmapheresis results in prolonged reduction of HLA antibodies while leaving protective immunity intact.
One Lambda Inc., Canoga Park, CA, USA. meverly@onelambda.com
Matthew J
MJ
Everly
Paul I
PI
Terasaki
Judy
J
Hopfield
Hargovind L
HL
Trivedi
Hugo
H
Kaneku
D017209:Apoptosis; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D003131:Combined Modality Therapy; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007109:Immunity; D007074:Immunoglobulin G / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D010956:Plasmapheresis; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D011719:Pyrazines / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000276:immunology; D017211:Treatment Failure
D001897:Boronic Acids; D006680:HLA Antigens; D007074:Immunoglobulin G; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D003404:Creatinine; D046988:Proteasome Endopeptidase Complex