The Immunology of Transfusion Medicine: Past, Present, and Future

The identification of alloantigens has been central to understanding how polymorphic variation influences transfusion safety through potential immune incompatibilities between individuals. Patients may possess naturally occurring antibodies that develop within the first few months of life or form alloantibodies after exposure to alloantigens during transfusion or pregnancy. These antibodies complicate the search for compatible blood and increase the risk of hemolytic disease of the fetus and newborn, as well as fetal and neonatal thrombocytopenia. Alloimmune mechanisms can also contribute to transfusion-related acute lung injury and transfusion-associated graft-versus-host disease. Beyond the direct complications of alloimmunity, changes in the metabolic and immunologic characteristics of transfused blood products can affect recipient immune function. In this review, we explore the historical interplay between immunology and transfusion medicine and highlight emerging preclinical and clinical insights into the field, with particular focus on the development and clinical implications of red blood cell alloimmunization.