PMID- 22202499
OWN - NLM
STAT- MEDLINE
DCOM- 20120604
LR  - 20151119
IS  - 1542-6270 (Electronic)
IS  - 1060-0280 (Linking)
VI  - 46
IP  - 1
DP  - 2012 Jan
TI  - Lung transplantation across donor-specific anti-human leukocyte antigen 
      antibodies: utility of bortezomib therapy in early graft dysfunction.
PG  - e2
LID - 10.1345/aph.1Q509 [doi]
AB  - OBJECTIVE: To report the usefulness of bortezomib therapy in a sensitized lung 
      transplant recipient experiencing antibody-mediated rejection. CASE SUMMARY: 
      During a pretransplant evaluation, a 62-year-old woman with usual interstitial 
      pneumonitis developed a diverticular bleed requiring transfusions, which elevated 
      her panel reactive antibody to 98% for human leukocyte antigen (HLA) class I and 
      71% for class II. She underwent desensitization to decrease her panel reactive 
      antibody levels. She received a double lung transplant across a weak HLA class II 
      incompatibility but developed respiratory failure due to early graft dysfunction. 
      On postoperative day (POD) 14 she was found to have donor-specific antibodies 
      (DSA) to HLA class I and class II antigens. She received intravenous 
      immunoglobulin (IVIG), plasmapheresis, and bortezomib to reduce the DSA. Repeat 
      DSA testing on POD 80 demonstrated a 50% reduction in DSA, which became 
      undetectable at POD 255. DISCUSSION: Antibody-mediated rejection (AMR) is 
      difficult to diagnose and treat in lung transplantation. Since primary treatment 
      options such as plasmapheresis and IVIG alone may not adequately eradicate DSA, 
      the proteasome inhibitor bortezomib can be of additional value for the treatment 
      of AMR. Bortezomib causes apoptosis of plasma cells, thus eliminating the 
      production of allograft-specific DSA. CONCLUSIONS: This is the first report 
      describing the utility of bortezomib for early graft dysfunction in a highly 
      sensitized lung transplant recipient. Although this patient had preformed 
      donor-specific anti-HLA antibodies, AMR was successfully treated with a 
      combination of plasmapheresis, IVIG, and bortezomib. At time of writing, the 
      patient continued to have excellent graft function 2 years posttransplant. 
      Bortezomib is a potent inhibitor of plasma cell production and it appears to be 
      useful for the treatment of antibody-mediated graft dysfunction.
FAU - Stuckey, Linda J
AU  - Stuckey LJ
AD  - Department of Pharmacy Services, University of Michigan Health Systems, Ann 
      Arbor, MI, USA. indastu@med.umich.edu
FAU - Kamoun, Malek
AU  - Kamoun M
FAU - Chan, Kevin M
AU  - Chan KM
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20111227
PL  - United States
TA  - Ann Pharmacother
JT  - The Annals of pharmacotherapy
JID - 9203131
RN  - 0 (Boronic Acids)
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
SB  - IM
MH  - Boronic Acids/administration & dosage/immunology/*therapeutic use
MH  - Bortezomib
MH  - Female
MH  - Graft Rejection/immunology/*prevention & control
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Isoantibodies/*blood/immunology
MH  - Lung Transplantation/*immunology
MH  - Middle Aged
MH  - Protease Inhibitors/administration & dosage/immunology/*therapeutic use
MH  - Pyrazines/administration & dosage/immunology/*therapeutic use
MH  - Tissue Donors
MH  - Treatment Outcome
EDAT- 2011/12/29 06:00
MHDA- 2012/06/05 06:00
CRDT- 2011/12/29 06:00
PHST- 2011/12/29 06:00 [entrez]
PHST- 2011/12/29 06:00 [pubmed]
PHST- 2012/06/05 06:00 [medline]
AID - aph.1Q509 [pii]
AID - 10.1345/aph.1Q509 [doi]
PST - ppublish
SO  - Ann Pharmacother. 2012 Jan;46(1):e2. doi: 10.1345/aph.1Q509. Epub 2011 Dec 27.