Proteasome inhibitor therapy for antibody-mediated rejection

被引:26
|
作者
Woodle, E. S. [1 ]
Walsh, R. C. [1 ]
Alloway, R. R. [2 ]
Girnita, A. [3 ]
Brailey, P. [3 ]
机构
[1] Univ Cincinnati, Dept Surg, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Div Nephrol, Cincinnati, OH 45267 USA
[3] Univ Cincinnati, Hoxworth Blood Ctr, Dept Transplant Immunol, Cincinnati, OH 45267 USA
关键词
humoral immunity; anti-HLA antibody; antibody mediated rejection; B cells; kidney transplant; heart transplant; proteasome inhibitor; UNFOLDED PROTEIN RESPONSE; DONOR-SPECIFIC ANTIBODIES; SOLID-ORGAN TRANSPLANTATION; CELL-CYCLE ARREST; MULTIPLE-MYELOMA; PLASMA-CELLS; RENAL-TRANSPLANTATION; ENDOPLASMIC-RETICULUM; B-CELLS; BORTEZOMIB;
D O I
10.1111/j.1399-3046.2011.01543.x
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
AMR is being recognized with increasing efficiency, but continues to present a significant threat to renal allograft survival. Traditional therapies for AMR (IVIG, plasmapheresis, rituximab, and antilymphocyte preparations) in general have provided inconsistent results and do not deplete the source of antibody production, viz., the mature plasma cell. Recently, the first plasma cell-targeted therapy in humans has been developed using bortezomib (a first in class PI) for AMR treatment in kidney transplant recipients. Initial experience with bortezomib involved treatment of refractory AMR. Subsequently, the efficacy of bortezomib in primary therapy for AMR was demonstrated. In a multicenter collaborative effort, the initial results with bortezomib in AMR have been confirmed and expanded to pediatric and adult heart transplant recipients. More recently, results from a prospective, staged desensitization trial has shown that bortezomib alone can substantially reduce anti-HLA antibody levels. These results demonstrate the significant potential of proteasome inhibition in addressing humoral barriers. However, the major advantage of proteasome inhibition lies in the numerous potential strategies for achieving synergy.
引用
收藏
页码:548 / 556
页数:9
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