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A small allelic variant in donor class I MHC is sufficient to induce alloantibodies following transfusion of standard or pathogen-reduced platelets in mice.
- Source :
-
Vox sanguinis [Vox Sang] 2020 Jul; Vol. 115 (5), pp. 367-376. Date of Electronic Publication: 2020 Mar 23. - Publication Year :
- 2020
-
Abstract
- 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.<br />Materials and Methods: C57BL/6 (B6) K <superscript>bm1</superscript> and B6 IA <superscript>bm12</superscript> mice with small variants in the class I K <superscript>b</superscript> and class II IA <superscript>b</superscript> 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.<br />Results: Both the K <superscript>bm1</superscript> and IA <superscript>bm12</superscript> alleles induced antibody responses, though the response to K <superscript>bm1</superscript> was greater. Pathogen reduction blocked the antibody responses to IA <superscript>bm12</superscript> , but not to K <superscript>bm1</superscript> . Both the K <superscript>bm1</superscript> and IA <superscript>bm12</superscript> alleles primed ex vivo cytokine responses that were blocked with pathogen reduction, though responses to IA <superscript>bm12</superscript> were broader and larger (K <superscript>bm1</superscript> responses: IFN-γ, TNFα, and MIP-1β; IA <superscript>bm12</superscript> responses: IFN-γ, TNFα, IL-1β, IL-10, IL-13, and GM-CSF). Pathogen-reduced K <superscript>bm1</superscript> PRP did not appear to induce any tolerance to subsequent untreated K <superscript>bm1</superscript> PRP transfusions.<br />Conclusion: Minor allelic variants in both the class I and class II MHC are capable of inducing an alloresponse to transfusion. The K <superscript>bm1</superscript> 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.<br /> (© 2020 International Society of Blood Transfusion.)
Details
- Language :
- English
- ISSN :
- 1423-0410
- Volume :
- 115
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Vox sanguinis
- Publication Type :
- Academic Journal
- Accession number :
- 32201962
- Full Text :
- https://doi.org/10.1111/vox.12897