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Recent reports indicate use of biotin\u2010labeled RBC (BioRBC) to determine red cell survival (RCS) offers substantial advantages over <jats:sup>51<\/jats:sup>Cr and other labeling methods. Occasional induction of BioRBC antibodies has been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>To investigate the causes and consequences of BioRBC immunization, we reexposed three previously immunized adults to BioRBC and evaluated the safety, antibody emergence, and RCS of BioRBC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BioRBC re\u2010exposure caused an anamnestic increase of plasma BioRBC antibodies at 5\u20137\u2009days; all were subclass IgG<jats:sub>1<\/jats:sub> and neutralized by biotinylated albumin, thus indicating structural specificity for the biotin epitope. Concurrently, specific antibody binding to BioRBC was observed in each subject. As biotin label density increased, the proportion of BioRBC that bound increased antibody also increased; the latter was associated with proportional accelerated removal of BioRBC labeled at density 6\u2009\u03bcg\/mL. In contrast, only one of three subjects exhibited accelerated removal of BioRBC density 2\u2009\u03bcg\/mL. No adverse clinical or laboratory events were observed. Among three control subjects who did not develop BioRBC antibodies following initial BioRBC exposure, re\u2010exposure induced neither antibody emergence nor accelerated BioRBC removal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We conclude re\u2010exposure of immunized subjects to BioRBC can induce anamnestic antibody response that can cause an underestimation of RCS. To minimize chances of antibody induction and underestimation of RCS, we recommend an initial BioRBC exposure volume of \u226410\u2009mL and label densities of \u226418\u2009\u03bcg\/mL.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.16849","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T09:15:51Z","timestamp":1646990151000},"page":"770-782","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antibodies against biotin\u2010labeled red blood cells can shorten <scp>posttransfusion<\/scp> survival"],"prefix":"10.1111","volume":"62","author":[{"given":"Donald M.","family":"Mock","sequence":"first","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology and the Department of Pediatrics University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1130-9551","authenticated-orcid":false,"given":"Sean R.","family":"Stowell","sequence":"additional","affiliation":[{"name":"Center for Transfusion and Cellular Therapies, Departments of Pathology and Laboratory Medicine and Pediatrics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Franco","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana V.","family":"Kyosseva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology and the Department of Pediatrics University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demet","family":"Nalbant","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics University of Iowa College of Pharmacy  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics The University of Iowa, Roy J. and Lucille A. 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