Development of a recombinant anti-Vel immunoglobulin M to identify Vel-negative donors.

Autor: van der Rijst MVE; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, AUMC, Amsterdam, The Netherlands.; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, AUMC, Amsterdam, The Netherlands., Lissenberg-Thunnissen SN; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, AUMC, Amsterdam, The Netherlands., Ligthart PC; Department of Immunohematology Diagnostic Services, Sanquin, Amsterdam, The Netherlands., Visser R; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, AUMC, Amsterdam, The Netherlands., Jongerius JM; Department of Research and Lab Services, National Screening Laboratory Sanquin, Sanquin, Amsterdam, the Netherlands., Voorn L; Department of Research and Lab Services, National Screening Laboratory Sanquin, Sanquin, Amsterdam, the Netherlands., Veldhuisen B; Department of Immunohematology Diagnostic Services, Sanquin, Amsterdam, The Netherlands., Vidarsson G; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, AUMC, Amsterdam, The Netherlands., van den Akker E; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, AUMC, Amsterdam, The Netherlands., van der Schoot CE; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, AUMC, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Transfusion [Transfusion] 2019 Apr; Vol. 59 (4), pp. 1359-1366. Date of Electronic Publication: 2019 Jan 31.
DOI: 10.1111/trf.15147
Abstrakt: Background: Alloimmunization against the high-frequency Vel blood group antigen may result in transfusion reactions or hemolytic disease of fetus and newborn. Patients with anti-Vel alloantibodies require Vel-negative blood but Vel-negative individuals are rare (1:4000). Identification of Vel-negative donors ensures availability of Vel-negative blood; however, accurate Vel blood group typing is difficult due to variable Vel antigen expression and limited availability of anti-Vel typing sera. We report the production of a recombinant anti-Vel that also identifies weak Vel expression.
Study Design and Methods: A recombinant anti-Vel monoclonal antibody was produced by cloning the variable regions from an anti-Vel-specific B cell isolated from an alloimmunized patient into a vector harboring the constant regions of immunoglobulin (Ig)G1-kappa or IgM-kappa. Antibody Vel specificity was tested by reactivity to SMIM1-transfected HEK293T cells and by testing various red blood cells (RBCs) of donors with normal, weak, or no Vel expression. High-throughput donor screening applicability was tested using an automated blood group analyzer.
Results: A Vel-specific IgM class antibody was produced. The antibody was able to distinguish between Vel-negative and very weak Vel antigen-expressing RBCs by direct agglutination and in high-throughput settings using a fully automated blood group analyzer and performed better than currently used human anti-Vel sera. High-throughput screening of 13,288 blood donations identified three new Vel-negative donors.
Conclusion: We generated a directly agglutinating recombinant anti-Vel IgM, M3F5S-IgM, functional in manual, automated agglutination assays and flow cytometry settings. This IgM anti-Vel will improve diagnostics by facilitating the identification of Vel-negative blood donors.
(© 2019 AABB.)
Databáze: MEDLINE