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

Marea V. E. van der Rijst, Suzanne N. Lissenberg-Thunnissen, Peter C. Ligthart, Remco Visser, John M. Jongerius, Lesley Voorn, Barbera Veldhuisen, Gestur Vidarsson, Emile van den Akker, C. Ellen van der Schoot

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1359-1366
Number of pages8
JournalTransfusion
Volume59
Issue number4
DOIs
Publication statusPublished - 2019

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