Immunomodulatory aspects of transfusion: a once and future risk?

BLOOD is good for you. What Goethe described as “ein ganz besonderer Saft” is the very stuff of life. It is not blood but other people’s blood that worries us. We have good reason for this concern. For more than 300 years, the therapeutic promise of blood transfusion has been tempered by the recognition of adverse reactions, often mild, but occasionally acute, dramatic, and lethal. The public hears daily how hepatitis and human immunodeficiency viruses (HIV) continue to spread, despite the best efforts of public health authorities. Unfortunately, blood transfusion played a highly visible, if greatly exaggerated, role in these epidemics. Now an additional transfusion-related threat seems to be emerging. Evidence from a variety of sources suggests that allogeneic blood alters the immune response in a way that may render the recipient vulnerable to infection, the recurrence of malignancy, or the reactivation of latent viruses. This phenomenon has been termed the immunomodulatory effect of blood transfusion. Few current practitioners appreciate that during the first half of the 20th century the major risks of transfusion were immunologic, not infectious. Incredibly, lifethreatening hemolytic transfusion reactions, now occurring about once in every 600,000 units transfused, occurred about once in every 500 transfusions earlier in this century. Transfusion safety improved in parallel with our understanding of the humoral immune system. Landsteiner’s description of the major blood groups in 1900 removed the dominant immunologic barrier to transfusion and provided the theoretical basis for understanding red cell compatibility. Later, a crude agglutination assay, the antiglobulin (Coombs) tests, furnished the tools for identifying other clinically important antigens expressed on the red-cell membrane. Antiglobulin testing proved critical for detecting alloantibodies, diagnosing hemolytic transfusion reactions, providing serologically compatible blood, and understanding and preventing most cases of hemolytic disease of the newborn. Similar assays defined the platelet and leukocyte antigens that were responsible for post-transfusion febrile reactions and immune refractoriness to platelet transfusion. By the last quarter of the century, most clinicians believed that the immunologic complications of blood transfusion were well understood if not largely solved. Ironically, as knowledge about the mechanisms of immune responsiveness and tolerance evolves, and as tools to measure alterations in immunity become available, additional immunologic consequences of blood transfusion are being detected. Numerous alterations in circulating blood cells have been reported in patients transfused with allogeneic blood. These changes include decreased numbers of circulating lymphocytes, modifications in the T-cell helper/suppressor ratio, changes in B-cell function, down-regulation of antigen-presenting cells, and activation of immune cells as measured by a number of cell surface markers. Some of these changes persist for months or even longer after transfusion. The lingering question has been whether these observations represent no more than laboratory curiosities, or * Chief.