Lung Transplantation Across Donor-Specific Anti-Human Leukocyte Antigen Antibodies: Utility of Bortezomib Therapy in Early Graft Dysfunction

Abstract

To report the usefulness of bortezomib therapy in a sensitized lung transplant recipient experiencing antibody-mediated rejection. 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. 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. 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.