PMID- 22326708
OWN - NLM
STAT- MEDLINE
DCOM- 20120907
LR  - 20151119
IS  - 1878-5492 (Electronic)
IS  - 0966-3274 (Linking)
VI  - 26
IP  - 4
DP  - 2012 Jun
TI  - Proteasome inhibition by bortezomib: effect on HLA-antibody levels and 
      specificity in sensitized patients awaiting renal allograft transplantation.
PG  - 171-5
LID - 10.1016/j.trim.2012.01.002 [doi]
AB  - BACKGROUND: Sensitization to human leukocyte antigen (HLA) prolongs waiting list 
      time and reduces allograft survival in solid organ transplantation. Current 
      strategies for pretransplant desensitization are based on B-cell depletion and 
      extracorporeal treatment. The proteasome inhibitor bortezomib allows direct 
      targeting of the antibody-producing plasma cell and has been used in 
      antibody-mediated rejection (AMR) and recipient desensitization with varying 
      results. Here, we report the effect of bortezomib preconditioning on HLA antibody 
      titers and specificity in highly sensitized patients awaiting renal allograft 
      transplantation. PATIENTS AND METHODS: Two highly sensitized patients awaiting 
      third kidney transplantation were given one cycle of bortezomib (1.3 mg/m(2), days 
      1, 4, 8, 11), as part of recipient desensitization. Time-course and levels of 
      anti-HLA antibodies, as well as specificity to previous transplant antigens were 
      monitored by luminex technology. In addition, measles and tetanus toxoid 
      immunoglobulin G (IgG) was measured. RESULTS: Following bortezomib, overall 
      changes in IgG levels were small and no sustained reduction in anti-HLA class I 
      or II antibody levels was observed over more than 100 days of follow-up to both, 
      donor specific and non-donor specific antigens. Moreover, anti-measles and 
      -tetanus toxoid IgG levels remained unchanged. CONCLUSIONS: Bortezomib 
      preconditioning alone does not result in sustained reduction of HLA antibody 
      levels or alter protective immunity in sensitized patients. This supports the 
      notion, that bortezomib requires activation of plasma cells, as in AMR, to 
      effectively reduce HLA antibody production. Hence, in a pretransplant setting, 
      combination strategies may be required to derive benefit from proteasome 
      inhibition.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Guthoff, Martina
AU  - Guthoff M
AD  - Department of Endocrinology and Diabetology, Angiology, Nephrology and Clinical 
      Chemistry, Otfried-Muller-Str. 10, 72076 Tubingen, Germany.
FAU - Schmid-Horch, Barbara
AU  - Schmid-Horch B
FAU - Weisel, Katja C
AU  - Weisel KC
FAU - Haring, Hans-Ulrich
AU  - Haring HU
FAU - Konigsrainer, Alfred
AU  - Konigsrainer A
FAU - Heyne, Nils
AU  - Heyne N
LA  - eng
PT  - Journal Article
DEP - 20120202
PL  - Netherlands
TA  - Transpl Immunol
JT  - Transplant immunology
JID - 9309923
RN  - 0 (Boronic Acids)
RN  - 0 (Epitopes)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
SB  - IM
MH  - Boronic Acids/*administration & dosage/adverse effects
MH  - Bortezomib
MH  - Epitopes/metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - Graft Rejection/etiology/prevention & control
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Immunity, Humoral
MH  - Immunization
MH  - Immunoglobulin G/blood/immunology
MH  - Kidney Transplantation/*immunology
MH  - Lymphocyte Activation/drug effects
MH  - Male
MH  - Plasma Cells/*drug effects/immunology
MH  - Proteasome Inhibitors
MH  - Pyrazines/*administration & dosage/adverse effects
MH  - Reoperation
MH  - *Transplantation Conditioning
EDAT- 2012/02/14 06:00
MHDA- 2012/09/08 06:00
CRDT- 2012/02/14 06:00
PHST- 2011/12/28 00:00 [received]
PHST- 2012/01/17 00:00 [revised]
PHST- 2012/01/18 00:00 [accepted]
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2012/09/08 06:00 [medline]
AID - S0966-3274(12)00011-1 [pii]
AID - 10.1016/j.trim.2012.01.002 [doi]
PST - ppublish
SO  - Transpl Immunol. 2012 Jun;26(4):171-5. doi: 10.1016/j.trim.2012.01.002. Epub 2012 
      Feb 2.