A small allelic variant in donor class I MHC is sufficient to induce alloantibodies following transfusion of standard or pathogen-reduced platelets in mice.

BACKGROUND AND OBJECTIVES

Alloimmunization targeting major histocompatibility (MHC) antigens is common following platelet transfusion. Pathogen reduction of platelets can block alloimmunization to MHC in mice and induce partial antigen-specific tolerance to subsequent transfusions. This study utilized small allelic variants to evaluate the relative contributions of class I and class II MHC to the alloresponse against untreated or pathogen-reduced platelets.

MATERIALS AND METHODS

C57BL/6 (B6) K and B6 IA mice with small variants in the class I K and class II IA alleles, respectively, were used as platelet donors for wild-type B6 recipients. Both untreated and pathogen-reduced platelet-rich plasma (PRP) transfusions were evaluated for immunogenicity by measuring antibody responses and ex vivo cytokine production.

RESULTS

Both the K and IA alleles induced antibody responses, though the response to K was greater. Pathogen reduction blocked the antibody responses to IA , but not to K . Both the K and IA alleles primed ex vivo cytokine responses that were blocked with pathogen reduction, though responses to IA were broader and larger (K responses: IFN-γ, TNFα, and MIP-1β; IA responses: IFN-γ, TNFα, IL-1β, IL-10, IL-13, and GM-CSF). Pathogen-reduced K PRP did not appear to induce any tolerance to subsequent untreated K PRP transfusions.

CONCLUSION

Minor allelic variants in both the class I and class II MHC are capable of inducing an alloresponse to transfusion. The K PRP induced alloantibodies even with pathogen reduction and did not show signs of inducing the partial tolerance to subsequent transfusions observed with a larger MHC mismatch.