HLA-Homozygous Donors and Transfusion-Associated Graft-versus-Host Disease

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Abstract
In the July 6 issue, Thaler et al. present two fascinating cases of catastrophic transfusion-associated graft-versus-host disease occurring after open-heart surgery.1 However, I must disagree with their assertion that "cardiac surgery in itself does not render the patient immunodeficient." On the contrary, it has been well documented that for about the first week after open-heart surgery, patients have profound lymphopenia2 as well as functional deficits associated with T-cell immunity3 4 5 — more so than patients undergoing other types of surgery.2 , 5 The phenomenon appears to be associated with the use of the cardiopulmonary-bypass pump, although the mechanism is unclear. The lymphopenia mainly affects T lymphocytes of the T-helper (CD4+) class,5 6 7 8 9 particularly the T-helper/inducer (CD4+,CDw29+ ) subclass.9 This subclass is responsible for inducing B lymphocytes10 and, perhaps more important, cytotoxic CD8+ T lymphocytes.11 Indeed, viral postperfusion syndromes occur not infrequently after cardiopulmonary bypass,12 and the excess of patients who have had open-heart surgery that appears in the registry of cases of transfusion-associated acquired immunodeficiency syndrome (AIDS) maintained by the Centers for Disease Control has been attributed to the immune dysfunction associated with cardiopulmonary bypass.5 This excess could be explained by the failure of the CD4+,CDw29+ subset to induce cytotoxic CD8+ T-cell antiviral response during and shortly after cardiopulmonary bypass, with a consequent higher efficiency of HIV infection when the contaminated blood product is administered during that critical period. In the same way, both viral postperfusion syndrome and transfusion-associated graft-versus-host disease in patients who have had open-heart surgery can be understood as the consequences of transient cardiopulmonary-bypass—induced immunodeficiency. In this context, the admonition of Thaler et al. against transfusions with nonirradiated blood products, which contain immunocompetent graft lymphocytes, is well taken and justified for the theoretical reasons outlined here.