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 ^bm1 and B6 IA ^bm12 mice with small variants in the class I K ^b and class II IA ^b 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 ^bm1 and IA ^bm12 alleles induced antibody responses, though the response to K ^bm1 was greater. Pathogen reduction blocked the antibody responses to IA ^bm12 , but not to K ^bm1 . Both the K ^bm1 and IA ^bm12 alleles primed ex vivo cytokine responses that were blocked with pathogen reduction, though responses to IA ^bm12 were broader and larger (K ^bm1 responses: IFN-γ, TNFα, and MIP-1β; IA ^bm12 responses: IFN-γ, TNFα, IL-1β, IL-10, IL-13, and GM-CSF). Pathogen-reduced K ^bm1 PRP did not appear to induce any tolerance to subsequent untreated K ^bm1 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 ^bm1 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.
(© 2020 International Society of Blood Transfusion.)