Discipline of Hematology Transfusion and Cell Therapy, University of São Paulo School of Medicine (FMUSP), São Paulo, Brazil.
Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, Brazil.
Transfusion. 2019 May;59(5):1827-1835. doi: 10.1111/trf.15202. Epub 2019 Feb 18.
As CD38 is expressed on red blood cells (RBCs), the plasma of patients on daratumumab (DARA) reacts with the panel cells of pretransfusion tests, masking underlying alloantibodies. The treatment of RBCs with dithiothreitol (DTT) is the most disseminated method to overcome DARA effect on immunohematological tests, but it hampers the identification of potentially harmful antibodies. Our goal was to validate a new strategy, the blockage monoclonal antibody protocol (BMAP), to mitigate the DARA interference on RBCs using anti-CD38 and antihuman globulin.
Samples of patients receiving DARA were included in the study. Sera were tested using both DTT- and BMAP-treated RBCs, which comprised three steps: 1) titration of monoclonal anti-CD38, 2) treatment of RBCs obtained from donors with anti-CD38, and 3) blockage of anti-CD38-adsorbed RBCs with antihuman globulin.
Twenty patients were included in the study. Donor RBCs were treated with anti-CD38 and successfully blocked with antihuman globulin. In 19 patients, DARA-mediated agglutination was eliminated using both DTT- and BMAP-treated RBCs. In one patient, agglutination persisted when tested against the BMAP-treated RBCs, and alloantibodies were identified. Patient samples were mixed with commercial anti-D, -C, -e, -K, -Jka, -Kpb and tested against antigen-positive BMAP-treated RBCs, resulting in detection of these antibodies.
This study validated a new strategy to minimize the interference of DARA on immunohematological tests. The protocol preserves the integrity of RBC antigens, permitting the detection of antibodies from all blood group systems. The BMAP has potential use in other situations where specific antibodies may interfere with pretransfusion screening.
由于 CD38 表达于红细胞（RBC）上，接受达雷妥尤单抗（DARA）治疗的患者的血浆会与输血前检测用的试剂细胞发生反应，从而掩盖潜在的同种异体抗体。用二硫苏糖醇（DTT）处理 RBC 是克服 DARA 对免疫血液学检测影响最广泛的方法，但它会阻碍潜在有害抗体的鉴定。我们的目标是验证一种新策略，即阻断单克隆抗体方案（BMAP），使用抗-CD38 和抗人球蛋白来减轻 DARA 对 RBC 的干扰。
本研究纳入了正在接受 DARA 治疗的患者的样本。血清分别用 DTT 和 BMAP 处理的 RBC 进行检测，包括三个步骤：1）单克隆抗-CD38 的滴定，2）用抗-CD38 处理来自供体的 RBC，3）用抗人球蛋白阻断抗-CD38 吸附的 RBC。
本研究纳入了 20 名患者。用抗-CD38 处理供体 RBC，并成功用抗人球蛋白阻断。在 19 名患者中，DTT 和 BMAP 处理的 RBC 均消除了 DARA 介导的凝集。在 1 名患者中，用 BMAP 处理的 RBC 检测时凝集仍然存在，并鉴定出同种异体抗体。将患者样本与商业抗-D、-C、-e、-K、-Jka、-Kpb 混合，并用抗原阳性的 BMAP 处理的 RBC 进行检测，从而检测到这些抗体。
本研究验证了一种新策略，以最大限度地减少 DARA 对免疫血液学检测的干扰。该方案保留了 RBC 抗原的完整性，允许检测所有血型系统的抗体。BMAP 可能在其他可能因特定抗体而干扰输血前筛查的情况下使用。
