Beyond Histology: Lowering Human Leukocyte Antigen Antibody to Improve Renal Allograft Survival in Acute Rejection

Terasaki Foundation Laboratory, Los Angeles, CA 90064, USA.
Transplantation (Impact Factor: 3.83). 04/2010; 89(8):962-7. DOI: 10.1097/TP.0b013e3181cbac02
Source: PubMed


The common endpoint in the treatment of antibody-mediated rejection (AMR) is functional reversal (creatinine levels). Reduction of human leukocyte antigen (HLA) antibody strength is not commonly considered as an essential endpoint for AMR resolution. The purpose of this study was to determine whether reduction in HLA antibody intensity in patients with histologic AMR reversal influences long-term renal allograft survival.
Renal allograft recipients were included if he or she had a biopsy diagnosis of AMR (between August 2000 and October 2008) and serial evaluation for HLA antibodies prebiopsy and postbiopsy. Antibody reduction was defined as mean fluorescence intensity decrease more than 50% in highest intensity antibody after AMR therapy and the absence of new antibody formation. Patients were treated with plasmapheresis, thymoglobulin/OKT3, and corticosteroids. Survival analysis was performed using STATA/MP v10 (College Station, TX).
Twenty-eight patients were analyzed. Antibody reduction failed to occur in 22 of 28 cases. Baseline characteristics were similar between groups. Antibody nonresponders had significantly shorter allograft survival time (61.4 months) compared with antibody responders (no failures) (P=0.04, log-rank test).
In conclusion, failure to significantly reduce antibody levels and prevent new formation was strongly predictive of allograft loss. This observation suggests that the therapeutic intervention that reduces antibody production may prolong graft survival in transplantation.

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    • "Insufficient reduction or suppression of pre-formed HLA-DSA before KT can result in a hyper-acute or acute antibody mediated rejection (AAMR) (1). In addition, development of HLA-DSA after KT can induce not only acute but also chronic AMR, which could be associated with poor allograft survival (2). For these reasons, research has focused on protocol development to effectively suppress the humoral immune system in kidney transplant recipients (3). "
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    ABSTRACT: This study aimed to investigate the effect of bortezomib in the desensitization and treatment of acute antibody mediated rejection (AAMR) in kidney transplantation. Nine patients who received bortezomib therapy for desensitization (DSZ group, n = 3) or treatment of AAMR (AAMR group, n = 6) were included in this study. In the DSZ group, 2 patients required DSZ owing to positive cross match and 1 owing to ABO mismatch with high baseline anti-ABO antibody titer (1:1,024). Bortezomib was used at 1, 3, 8, and 11 days from the start of the treatment. In the AAMR group, 3 patients showed full recovery of allograft function after bortezomib use and decrease in donor specific anti-HLA antibody (HLA-DSA). However, 3 patients did not respond to bortezomib and experienced allograft failure. In the DSZ group, negative conversion of T-CDC (complement-dependent cytotoxicity) was achieved, and HLA-DSA was decreased to lower than a weak level (median fluorescence intensity [MFI] < 5,000) in 2 patients. In the case of ABO mismatch kidney transplantation, the anti-A/B antibody titer decreased to below the target (≤ 1:16) after bortezomib therapy. Therefore, bortezomib could be an alternative therapeutic option for desensitization and treatment of AAMR that is unresponsive to conventional therapies. Graphical Abstract
    Journal of Korean Medical Science 05/2014; 29(5):648-51. DOI:10.3346/jkms.2014.29.5.648 · 1.27 Impact Factor
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    • "In addition, the profile of the donor antibodies determined before the transplantation facilitates monitoring of the production of anti-HLA antibodies after transplantation. It also helps in assessing the effectiveness of immunosuppressive therapy in the cases of humoral rejection [6] [7]. Until recently, the level of allosensitization in patients on the Polish National Waiting List awaiting kidney transplantation was assessed by PRA CDC test only (Panel Reactive Antibodies Complement Dependent Cytotoxicity). "
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