Universal RBCs

Antigens on RBCs have been a problem for blood transfusion right from the start. In the mid-17th century, Jean Denis in France and Richard Lower in England attempted animal-to-human blood transfusions, only to be foiled by (among many factors) the presence of incompatibilities between the animal RBCs and human serum. James Blundell’s use of human-to-human blood transfusions in the early 19th century lowered the immunologic barrier, but major RBC antigenic differences between humans led to hemolytic reactions. With Landsteiner’s discovery of the ABO blood group antigens on RBCs and associated serum isoagglutinins a century ago,1 the major cause of this immune reaction had been found, and successful blood transfusion could be achieved. Blood samples from donor and patient were each tested and classified into one of the four phenotypes—O, A, B, or AB—which allowed the donor and patient phenotypes to be matched. At the turn of this new century, typing of ABO antigens still remains the critical step in RBC transfusion, necessitated by the presence of preexisting antibodies to A and/or B antigens in individuals lacking these antigens. The entire system of blood collection, distribution, and transfusion revolves around the ABO blood groups. Elimination of this need for typing, by the creation of a universal RBC for transfusion, would bring about a revolution in blood banking akin to that which followed Landsteiner’s discovery of the ABO blood group system. So what are the potential methods with which to accomplish this task? Will universal RBCs be coming to neighborhood blood centers and hospitals anytime soon? The term “universal RBC” could have several meanings. Group O persons are considered universal RBC donors because they lack the antigens of the ABO blood group system, and thus their RBCs can be transfused to any recipient without concern for preexisting ABO antibodies. Blood donor and recipient are also matched for D antigen, despite the lack of anti-D in nonimmunized recipients, because the immunization rate is greater than 50 percent upon exposure of D– recipients to the D antigen. Thus, O– could be considered the universal RBC. Finally, a small percentage of patients have preexisting antibodies to one or more of the several hundred additional antigens described on RBCs, so a truly universal RBC would have to be negative for all of these antigens. (This discussion is limited to universal RBCs; products such as Hb-based oxygen carriers are also universal, in that they can be transfused to any patient.) Two general approaches could be used to make a universal RBC. The RBC antigens can be removed permanently from the RBC surface, or they can be masked to avoid recognition by the immune system. This recognition by the immune system could lead to an immediate reaction via preexisting antibodies in the recipient against antigens on donor RBCs or to later alloimmunization to these antigens. There has been substantial progress along both of these research directions, yielding RBC products of differing characteristics and different potential uses in transfusion medicine.