Assessing and mitigating the interference ofALX148 , a novelCD47 blocking agent, in pretransfusion compatibility testing
| Autor: | Hein Hustinx, Hong I. Wan, Janet Sim, Mi Sook Yoon, Hyungsuk Kim, Tae Yeul Kim |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Therapeutic blockade Erythrocytes Immunology Antineoplastic Agents CD47 Antigen 030204 cardiovascular system & hematology Blood group antigens 03 medical and health sciences 0302 clinical medicine Humans Immunology and Allergy Compatibility testing Chemistry CD47 Antibody screening tests Hematology Immunoglobulin Fc Fragments Coombs Test Blood Grouping and Crossmatching Antigen typing Female Antibody screening Immediate spin 030215 immunology |
| Zdroj: | Transfusion. 60:2399-2407 |
| ISSN: | 1537-2995 0041-1132 |
| DOI: | 10.1111/trf.16009 |
| Popis: | ALX148, a novel CD47 blocking agent, is in clinical development for the treatment of advanced solid tumors and lymphoma. Because CD47 is highly expressed on red blood cells (RBCs), its therapeutic blockade can potentially interfere with pretransfusion compatibility testing. This study describes the interference of ALX148 in pretransfusion compatibility testing and evaluates the methods used for mitigating such interference. Study design and methods Routine serologic tests were performed on six samples from four patients treated with ALX148. Antibody screening tests were performed on ALX148-spiked plasma, and RBC testing including antigen typing was performed on ALX148-coated RBCs. Soluble CD47 or high-affinity signal regulatory protein α (SIRPα) monomers were used to remove the false-positive reactivity of ALX148-spiked plasma with or without anti-E. Results ALX148 caused false-positive reactivity in antibody screening using indirect antiglobulin testing (IAT) and two-stage papain testing. However, false-positive reactivity was not observed at the immediate spin (IS), room temperature (RT), and 37°C phases. Direct antiglobulin testing, autologous controls, and eluates showed positive results. ALX148 did not affect blood group antigen typing performed at the IS or RT phases. The use of 50- to 100-fold molar excess of soluble CD47 or 300-fold molar excess of high-affinity SIRPα monomers removed false-positive reactivity in IAT without affecting anti-E detection. Conclusion ALX148 generates false-positive reactivity in IAT, interfering with pretransfusion compatibility testing. The use of soluble CD47 or high-affinity SIRPα monomers can resolve the interference without possibly missing clinically significant alloantibodies. |
| Databáze: | OpenAIRE |
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