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논문분류	춘계학술대회 초록집
제목	DSA Monitoring & Treatment of Chronic Active Antibody Mediated Rejection
저자	Byung Ha Chung
출판정보	2022; 2022(1):
키워드
초록	In kidney transplantation, antibody-mediated allograft injury caused by donor HLA-specific antibodies (HLA-DSA) has recently been identified as one of the major causes of late graft loss. Indeed, circulating HLA-DSA are found in a substantial number of kidney allograft recipients, and the presence of these alloantibodies is significantly correlated with the development of allograft injury and later graft loss. In this regard, HLA-DSA is the most important biomarker routinely monitored with the frequency based on underlying immunologic risk. Appropriate assessment of HLA-DSA is critical for maximizing both long- and short-term allograft survival. Periodic routine screening for HLA-DSA based on immunologic risk, perhaps yearly or at the time of dysfunction in low-risk cases is recommended. More frequent monitoring is indicated in higher risk cases, such as those with pre-existing HLA-DSA or previously failed transplants. And it should be measured if there is graft dysfunction, immunosuppression minimization, or non-adherence. HLA-DSA may be preexisting at the time of implantation or develop de novo after transplantation. ABMR caused by preexisting HLA-DSA is termed type 1 and typically occur shortly after transplantation. de novo HLA-DSA cause type 2 ABMR, usually occur later, and showed chronic feature, so called chronic active antibody mediated rejection. Pre-existing HLA-DSA frequently become undetectable and type 1 ABMR is more amenable to antibody reduction therapy. Therefore, monitoring strategy is usually focusing on the de novo DSA, and also the importance of therapeutic strategy for cABMR caused by de novo DSA has been emerging. Indeed, the prognosis of CAMR is poor and conventional immunosuppressants mainly targeting T cell-mediated immunity cannot prevent or reverse it. Therefore, some researchers have suggested that additional therapies directed at the humoral response may be required for the treatment of cABMR. Some pilot studies have suggested that the combined use of rituximab (RTX) and intravenous immunoglobulin (IVIg) therapy may be useful for the treatment of cABMR. However, combination of IVIg and RTX was not useful in patients displaying transplant glomerulopathy and HLA-DSA in multicenter, prospective, randomized double blind trials. Bortezomib is proteasome inhibitor, and effectively suppress antibody producing plasma cells. However, the randomized trial of bortezomib in late antibody mediated rejection failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA. Recently, IL-6 targeting therapy has been proposed as a new strategy for the treatment of cABMR. In pilot study, tocilizumab, IL-6 receptor blocker stabilized allograft function in long term follow-up especially compared with historical published treatments. In another phase 2 clinical trial, clazakizumab, IL-6 inhibitor, decreased DSA and modulated rejection-related gene-expression patterns. Phase 3 randomized controlled trials about the usefulness of clazakizumab is in progress. We expect that the strategy to minimize allograft injury by HLA-DSA will continue to develop along with the development of immune monitoring methods and also development of effective therapeutics.
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