A Case of Panagglutination on Antibody Identification in a Multiple Myeloma Patient Receiving Daratumumab / 대한수혈학회지

Herein, we report a patient showing panagglutination in the unexpected antibody identification test after the administration of daratumumab. The patient was a 66-year-old woman who had undergone multiple cycles of chemotherapy and autologous peripheral blood stem cell transplantation for treating multiple myeloma; however, despite treatment, she had relapsed. Therefore, daratumumab, on clinical trials in Korea, started to be administered. After administration of daratumumab, the result of antibody screening test was positive, on the contrary to the result prior to the administration. Moreover, all positive reactions were shown in the antibody identification to the panel cells. After destroying CD38 antigens on the surface of RBCs using DTT, negative results were obtained. Daratumumab—a novel therapeutic human CD38 monoclonal antibody that can be used as targeted immunotherapy—is an FDA-approved drug for treating multiple myeloma. Because CD38 is expressed not only on myeloma cells, but also on red blood cells (RBCs), the use of daratumumab might lead to RBC agglutinations, and thereby resulting in false-positive results on the pre-transfusion tests. Therefore, caution is needed in case of a patient receiving daratumumab. Furthermore, additional test using DTT is required, especially when panagglutination was shown in the antibody identification test, as in this case.

The Inhibition of TREK2 Channel by an Oxidizing Agent, 5,5'-dithio- bis (2-nitrobenzoic acid), via Interaction with the C-terminus Distal to the 353rd Amino Acid

TREK (TWIK-RElated K+ channels) and TRAAK (TWIK-Related Arachidonic acid Activated K+ channels) were expressed in COS-7 cells, and the channel activities were recorded from inside-out membrane patches using holding potential of -40 mV in symmetrical 150 mM K+ solution. Intracellular application of an oxidizing agent, 5,5'-dithio-bis (2-nitrobenzoic acid) (DTNB), markedly decreased the activity of the TREK2, and the activity was partially reversed by the reducing agent, dithiothreitol (DTT). In order to examine the possibility that the target sites for the oxidizing agents might be located in the C-terminus of TREK2, two chimeras were constructed: TREK2 (1-383)/TASK3C and TREK2 (1-353)/TASK3C. The channel activity in the TREK2 (1-383)/TASK3C chimera was still inhibited by DTNB, but not in the TREK2 (1-353)/TASK3C chimera. These results indicate that TREK2 is inhibited by oxidation, and that the target site for oxidation is located between the amino acid residues 353 and 383 in the C-terminus of the TREK2 protein.