Transfusion in the age of molecular diagnostics

Abstract

DNA-based tests are increasingly being used to predict a blood group phenotype to improve transfusion medicine. This is possible because genes encoding 29 of the 30 blood group systems have been cloned and sequenced, and the molecular bases associated with most antigens have been determined. RBCs carrying a particular antigen, if introduced into the circulation of an individual who lacks that antigen (through transfusion or pregnancy), can elicit an immune response. It is the antibody from such an immune response that causes problems in clinical practice and the reason why antigen-negative blood is required for safe transfusion. The classical method of testing for blood group antigens and antibodies is hemagglutination; however, it has certain limitations, some of which can be overcome by testing DNA. Such testing allows conservation of antibodies for confirmation by hemagglutination of predicted antigen-negativity. High-throughput platforms provide a means to test relatively large numbers of donors, thereby opening the door to change the way antigen-negative blood is provided to patients and to prevent immunization. This review summarizes how molecular approaches, in conjunction with conventional hemagglutination, can be applied in transfusion medicine.During the 20 th century, knowledge of blood groups grew from three antigens [A, B, and O (later shown to be H)] to nearly 300 discrete antigens. Most blood group antigens are accommodated in 30 blood group systems, 1-3 and the gene (or a small gene family for MNS, Rh, and Ch/Rg systems) encoding each blood group system (the gene encoding P1 remains to be published) has been cloned and sequenced, 4 and the molecular bases associated with the vast majority of blood group antigens have been determined. 5 RBCs carrying a particular antigen can, if introduced into the circulation of an individual who lacks that antigen, elicit an immune response. It is the antibody from such an immune response that causes problems in clinical practice, such as in patient/donor blood transfusion incompatibility, maternal-fetal incompatibility, and autoimmune hemolytic anemia and the reason why antigen-negative blood is required for safe transfusion in these patients.The classical method of testing for blood group antigens and antibodies is hemagglutination. This technique has served the transfusion community well for decades, it is simple, requires little equipment, and when done correctly, has a specificity and sensitivity that is appropriate for the clinical care of the vast majority of patients requiring blood transfusion. However, hemagglutination, which is a subjective test, has certain limitations (Table 1). Collectively, the limitations have resulted in a relatively small number of donors being typed for a relatively small number of antigens, thereby limiting antigen-negative inventories.Correspondence Marion E. Reid, PhD, New York Blood Center, 310 E. 67th Street, New York, NY 10021; Phone: (212) The knowledge of the molecular bases associated with many blood group a...

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