The fate of anti-HLA antibody among renal transplantation recipients treated with bortezomib.
We present four cases of renal transplant recipients who were treated with bortezomib for four different indications, each of whom had circulating anti-HLA antibodies that were followed serially throughout their courses of bortezomib therapy. It is important to note that each patient was administered bortezomib in conjunction with other agents and therapies traditionally used for desensitization or the treatment of AMR. The results have been mixed. In some cases substantial decreases in HLA-antibody were temporally related to bortezomib therapy. In the one case of recalcitrant AMR there has been no reduction in DSA after 2 cycles of the drug. Bortezomib has been well tolerated. One patient developed reversible peripheral neuropathic pain while another experienced line sepsis, a urinary tract infection, and an invasive fungal skin infection. Again, this patient had also received protracted courses of plasmapheresis combined with T-cell and B-cell depleting agents. The use of these other drugs precludes the ability to rigorously evaluate the efficacy of bortezomib in isolation and points towards a need for large-scale, controlled trials to determine whether the drug's promising mechanism of action is applicable in the setting of solid organ transplantation.
The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Bonnie E
BE
Lonze
Nabil N
NN
Dagher
Christopher E
CE
Simpkins
Andrew L
AL
Singer
Dorry L
DL
Segev
Andrea A
AA
Zachary
Robert A
RA
Montgomery
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002102:Cadaver; D003404:Creatinine / Q000097:blood; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D014019:Tissue Donors
D001323:Autoantibodies; D001897:Boronic Acids; D006680:HLA Antigens; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; C069546:HLA-DQ7 antigen; D015395:Histocompatibility Antigens Class I; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D003404:Creatinine