Recipient inflammation affects the frequency and magnitude of immunization to transfused red blood cells

BACKGROUND: Most alloantigens on transfused red blood cells (RBCs) are weakly immunogenic, with only a 2 to 6 percent overall immunization rate even in patients receiving multiple transfusions. Although recipient genetics may contribute to responder and/or nonresponder status, in most cases HLA type does not predict humoral response to RBC antigens. In contrast, rates of alloimmunization do correspond to the underlying disease status of transfusion recipients, suggesting that acquired host factors may play an important role. In this context, it was hypothesized that the inflammatory status of a transfusion recipient would influence immunization to transfused RBCs. STUDY DESIGN AND METHODS: A novel murine model for alloimmunization to RBC antigens was developed with the mHEL mouse, which expresses hen egg lysozyme (HEL) as a model blood group antigen. Leukoreduced mHEL RBCs were transfused into wild-type recipient mice, and anti-HEL responses were monitored. To test the stated hypothesis, some recipient animals were injected with polyinosinic polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA molecule that induces viral-like inflammation. RESULTS: Similar to the immunogenicity of most RBC antigens in humans, transfusion of mHEL RBCs into uninflamed mice was only a weak immunogen. In contrast, poly(I:C)-treated mice had a significant increase in both the frequency and the magnitude of alloimmunization to the mHEL antigen. CONCLUSION: These findings demonstrate that recipient inflammation with poly(I:C) significantly enhances humoral immunization to transfused alloantigens in a murine model. Moreover, these data suggest that the inflammatory status of human transfusion recipients may regulate the immunogenicity of transfused RBCs.