CD38 Antibody Daratumumab for the Treatment of Chronic Active Antibody-mediated Kidney Allograft Rejection
CD38 Antibody Daratumumab for the Treatment of Chronic Active Antibody-mediated Kidney Allograft Rejection
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DOI：
10.1097/tp.0000000000003247
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发表时间：
2021-02-01
期刊：
影响因子：
6.2
通讯作者：
Boehmig, Georg A.
中科院分区：
文献类型：
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作者：
Doberer, Konstantin;Klaeger, Johannes;Boehmig, Georg A.
背景。晚期抗体介导的排斥反应（AMR）是移植失败的主要原因。潜在的治疗靶点是浆细胞和自然杀伤细胞（NK），它们都表达高水平的cd38。在这里，我们报告了在移植后13年诊断为阴烧骨髓瘤和抗hla II类供体特异性抗体阳性的慢性活动性AMR的肾移植受体中使用CD38单克隆抗体daratumumab（9个月的病程）。患者监测包括HLA单抗原检测，外周血免疫细胞表型，以及3个月和9个月的随访同种异体移植和骨髓活检，包括排斥相关基因表达模式的分析。结果：达拉单抗导致骨髓和血液中CD138（+）细胞持续耗竭，血液和移植组织中NK细胞计数显著降低。同时，血清中供者特异性抗体消失，骨髓中富集的CD138（+）细胞体外产生同种异体抗体也被取消。3个月的随访活检显示微循环炎症完全消退（g+ptc: 3 ~ 0）， AMR分子活性（AMR评分：0.79 ~ 0）
Background.Late antibody-mediated rejection (AMR) is a major cause of transplant failure. Potential therapeutic targets are plasma cells and natural killer (NK) cells, both expressing high levels of CD38.Methods.Here, we report the use of CD38 monoclonal antibody daratumumab (9-mo course) in a kidney allograft recipient diagnosed with smoldering myeloma and anti-HLA class II donor-specific antibody-positive chronic active AMR 13 years after transplantation. Patient monitoring included serial HLA single-antigen testing, peripheral blood immune cell phenotyping, as well as follow-up allograft and bone marrow biopsies at 3 and 9 months, including analyses of rejection-related gene expression patterns.Results.Daratumumab led to persistent CD138(+) cell depletion in the bone marrow and blood and substantially decreased NK cells counts in blood and graft tissue. At the same time, donor-specific antibody in serum disappeared, and in vitro alloantibody production by CD138(+) cells enriched from bone marrow aspirates was abrogated. A 3-month follow-up biopsy revealed a complete resolution of microcirculation inflammation (g+ptc: 3 to 0) and molecular AMR activity (AMR score: 0.79 to