Antibodies provoked by the transfusion of biotin-labeled red cells

Biotin-labeled (biotinylated) red cells (B-RBCs) offer a technique by which to study RBC volume and circulating kinetics without in vivo radiation. The immunogenicity of B-RBCs is undefined.

To determine if biotinylation renders RBCs immunogenic, autologous B-RBCs were transfused to 20 healthy subjects, and plasma samples were obtained before transfusion and serially for up to 6 months after transfusion. These serial samples, plus plasma from 20 normal control subjects not given B-RBCs, were screened for antibodies to B-RBCs by use of an antiglobulin technique against aliquots of group O RBCs from a single donor-one aliquot biotinylated and one aliquot not biotinylated (i.e., test and control RBCs). Posttransfusion recovery and survival of B-RBCs were also determined.

Plasma from none of 20 normal nontransfused subjects reacted with B-RBCs. Similarly, none of the 20 subjects given autologous B-RBC transfusions exhibited antibodies before transfusion. However, 3 of the 20 subjects transiently produced antibodies to B-RBCs after transfusion. Antibodies disappeared within 6 months in 2 of these 3 subjects and within 12 months in the third. Antibody reactivity was not reduced by dithiothreitol, but in 2 of the 3 subjects, B-RBC antibodies were neutralized by incubation with biotin solution. Circulating RBC kinetics were not altered in the 3 subjects with antibody. The significance of these observations is unclear, because antibodies were just beginning to emerge during the studies.

Biotinylation does not render RBCs reactive with normal human plasma (i.e., presumably does not evoke neoantigens). Transfused B-RBCs occasionally provoke IgG antibodies in healthy subjects. Because the biologic effects of B-RBC antibodies currently are unknown, testing for them is recommended when multiple B-RBC transfusions are given to study RBC volume or circulating kinetics.