In vitro affinity reduction of biologic response modifiers from production buffy coat platelets exposed to recombinant protein receptors

Transfusion
Per SandgrenJonas Axelsson

Abstract

Recent studies link biologic response modifiers found in donor platelet (PLT) concentrates to transfusion reactions. We tested a novel method to deplete BRMs from PLT concentrates using apheresis. Whole blood from 25 donors was treated to yield PLTs for in vitro measurements on Days 2, 5, and 7. On Day 7, PLTs were filtrated through columns with either antibody-coated agarose or rh-megalin bound to antibody-coated agarose. In addition, we also tested the naked matrix (agarose) and another apheresis surface containing rh-cubilin bound to agarose. Megalin and cubilin are parts of the protein complex mediating BRM endocytosis in the human kidney. Compared to before filtration (951 × 10(9)  ± 41 × 10(9) cells/L), PLT numbers decreased slightly after filtration over both naked (859 × 10(9)  ± 38 × 10(9) ) and antibody-coated (848 × 10(9)  ± 41 × 10(9) ) matrices (both p < 0.001 vs. before). Concentrations of interleukin (IL)-1β, IL-12 (p40), IL-12 (p70), and IL-7 all decreased by approximately 40% even in the absence of a recombinant surface. After filtration over rh-cubilin, but not rh-megalin, concentrations of IFN-γ, IL-1β, tumor necrosis factor-α, IL-12, and IL-7 all further decreased by 30% to 50%. In a pilot study of in vitro ...Continue Reading

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