PMID- 19461494
OWN - NLM
STAT- MEDLINE
DCOM- 20090708
LR  - 20220321
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 87
IP  - 10
DP  - 2009 May 27
TI  - Abrogation of anti-HLA antibodies via proteasome inhibition.
PG  - 1555-61
LID - 10.1097/TP.0b013e3181a4b91b [doi]
AB  - BACKGROUND: Current treatments for autoantibody-mediated diseases (i.e., systemic 
      lupus erythematosus) and alloantibodies (in transplant) are minimally effective. 
      Although they deplete naive B cells, plasmablasts, and transiently reduce 
      antibody concentrations, they are minimally effective against long-lived, 
      antibody-producing plasma cells. In transplantation, plasma cells produce 
      antibodies directed against human leukocyte antigen (HLA) antigens causing poor 
      allograft survival. We report the first clinical experience with a plasma cell 
      depleting therapy, bortezomib, to abrogate anti-HLA antibodies in transplantation 
      (outside of rejection) in an attempt to improve long-term allograft survival. 
      METHODS: Eleven patients with anti-HLA alloantibodies were treated with 
      bortezomib. All patients underwent plasmapheresis to aid in removal of antibodies 
      and to determine the effect of bortezomib. Serial measurements of anti-HLA 
      antibody levels were conducted weekly by single antigen bead on Luminex platform. 
      RESULTS: Bortezomib treatment elicited substantial reduction in both 
      donor-specific antibody (DSA) and non-DSA levels. Antibodies were directed 
      against DSA in 8 of 11 cases. Mean time to antibody appearance was 2 months 
      posttransplant. Within 22 days (median) from treatment initiation, 9 of 11 
      patients' antibody levels dropped to less than 1000 mean fluorescence intensity. 
      Of two patients without successful depletion, all had peak mean fluorescence 
      intensity more than 10,000. At a mean follow-up of approximately 4 months 
      posttreatment, all patients have stable graft function. Minimal transient side 
      effects were noticed with bortezomib in the form of gastrointestinal toxicity, 
      thrombocytopenia, and paresthesias. CONCLUSIONS: Bortezomib therapy effectively 
      abrogates anti-HLA antibodies. Hence, removal of antibodies, by proteasome 
      inhibition, represents a new treatment strategy for transplantation and may have 
      benefit in autoimmune-related disease.
FAU - Trivedi, Hargovind L
AU  - Trivedi HL
AD  - Department of Nephrology and Transplantation Medicine, Institute of Kidney 
      Diseases and Research Centre-Institute of Transplantation Sciences, Ahmedabad, 
      Gujarat, India. ikdrcad1@sancharnet.in
FAU - Terasaki, Paul I
AU  - Terasaki PI
FAU - Feroz, Aziz
AU  - Feroz A
FAU - Everly, Matthew J
AU  - Everly MJ
FAU - Vanikar, Aruna V
AU  - Vanikar AV
FAU - Shankar, Vangipurapu
AU  - Shankar V
FAU - Trivedi, Varsha B
AU  - Trivedi VB
FAU - Kaneku, Hugo
AU  - Kaneku H
FAU - Idica, Adam K
AU  - Idica AK
FAU - Modi, Pranjal R
AU  - Modi PR
FAU - Khemchandani, Sajani I
AU  - Khemchandani SI
FAU - Dave, Shruti D
AU  - Dave SD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Boronic Acids)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-D Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Isoantibodies)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Adult
MH  - Boronic Acids/immunology/therapeutic use
MH  - Bortezomib
MH  - Graft Rejection/*immunology
MH  - Graft Survival/*immunology
MH  - HLA Antigens/*immunology
MH  - HLA-D Antigens/immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - Isoantibodies/*blood/immunology
MH  - Kidney Transplantation/*immunology
MH  - Living Donors
MH  - Male
MH  - Protease Inhibitors/immunology/*therapeutic use
MH  - Proteasome Endopeptidase Complex/immunology
MH  - *Proteasome Inhibitors
MH  - Pyrazines/immunology/therapeutic use
MH  - Transplantation, Homologous/immunology
MH  - Young Adult
EDAT- 2009/05/23 09:00
MHDA- 2009/07/09 09:00
CRDT- 2009/05/23 09:00
PHST- 2009/05/23 09:00 [entrez]
PHST- 2009/05/23 09:00 [pubmed]
PHST- 2009/07/09 09:00 [medline]
AID - 00007890-200905270-00019 [pii]
AID - 10.1097/TP.0b013e3181a4b91b [doi]
PST - ppublish
SO  - Transplantation. 2009 May 27;87(10):1555-61. doi: 10.1097/TP.0b013e3181a4b91b.