Vicente Escamilla-Rivera, Yale University and his team found that Poly (I:C) causes failure of immunoprophylaxis to red blood cells expressing the KEL glycoprotein in mice. This study has been published on Blood in this April.
Polyclonal anti-D (RhIg) therapy has mitigated hemolytic disease of the newborn over the past half century, though breakthrough anti-D alloimmunization still occurs in some treated females.
Vicentes team hypothesized that antiviral responses may impact the efficacy of immunoprophylaxis therapy in a type 1 interferon (IFN)-dependent manner and tested this hypothesis in a murine model of KEL alloimmunization.Polyclonal anti-KEL immunoprophylaxis (KELIg) was administered to wild-type or knockout mice in the presence or absence of poly (I:C), followed by the transfusion of murine RBCs expressing the human KEL glycoprotein.
Anti-KEL alloimmunization, serum cytokines, and consumption of the transfused RBCs were evaluated longitudinally. In some experiments, recipients were treated with type 1 IFN (IFN-α/β). Recipient treatment with poly(I:C) led to breakthrough anti-KEL alloimmunization despite KELIg administration. Recipient CD4+ T-cells were not required for immunoprophylaxis efficacy at baseline, and modulation of the KEL glycoprotein antigen occurred to the same extent in the presence or absence of recipient inflammation. Under conditions where breakthrough anti-KEL alloimmunization occurred, KEL RBC consumption by inflammatory monocytes and serum MCP-1 and IL-6 were significantly increased. Poly(I:C) or type I IFN administration was sufficient to cause breakthrough alloimmunization, with poly(I:C) inducing alloimmunization even in the absence of recipient Type I interferon receptors.
A better understanding of how recipient antiviral responses lead to breakthrough alloimmunization despite immunoprophylaxis may have translational relevance to instances of RhIg failure that occur in humans.
Sherry
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