A complement-mediated rat xenotransfusion model of platelet refractoriness. (August 2020)

• Record Type: Journal Article
• Authors: Enos, Adrianne I.; Hair, Pamela S.; Krishna, Neel K.; Cunnion, Kenji M.
• Is Part Of: Molecular immunology. Volume 124(2020:Aug.)
• Page Start: 9
• Page End: 17
• Publication Date: 2020-08
• Subjects: ACD acid citrate dextrose -- HLA human leukocyte antigen -- HPA human platelet antigen -- ITP immune thrombocytopenia -- IVIG intravenous immune globulin -- NHS normal human serum -- PA-dPEG24 IALILEPICCQERAA-dPEG24 -- PIC1 peptide inhibitor of complement C1 -- SEM standard error of the means; Platelet refractoriness -- Complement -- PIC1; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.05.008
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Decreased platelet viability after sensitization and incubation with sera is inhibited Peptide Inhibitor of Complement C1. Wistar rat sera decreases human platelet viability which is partially reversible with a classical pathway complement inhibitor. A new animal model of platelet refractoriness was developed utilizing Wistar rats transfused with human platelets. Abstract: Background: Platelet refractoriness remains a challenging clinical dilemma although significant advancements have been made in identifying human leukocyte antigen (HLA) matched or HLA compatible units. Antiplatelet antibodies are the major risk factor for immune-mediated platelet refractoriness, yet the role of antibody-initiated complement-mediated platelet destruction remains poorly understood. Study Design and Methods: Human complement-mediated opsonization and killing of platelets was assayed ex vivo using antibody-sensitized human platelets incubated with complement-sufficient human sera. A new animal model of platelet refractoriness utilizing Wistar rats transfused with human platelets is described. Results: Human platelets sensitized with anti-platelet antibodies were rapidly opsonized with iC3b upon incubation in human sera. This opsonization could be completely blocked with a classical pathway complement inhibitor, PA-dPEG24. Complement activation decreased platelet viability, which was also reversible with complement inhibitor PA-dPEG24. A new rat model of platelet refractoriness was developed that demonstrated some platelet removal from the blood stream was complement mediated. Conclusions: Complement activation initiated by anti-platelet antibodies leads to complement opsonization and decreased platelet viability. A new rat model of platelet refractoriness was developed that adds a new tool for elucidating the mechanisms of platelet refractoriness.