Phagocytosis of platelets opsonized with differently glycosylated anti-HLA hIgG1 by monocyte-derived macrophages

Thijs L. J. van Osch, Juulke Steuten, Jan Nouta, Carolien A. M. Koeleman, Arthur E. H. Bentlage, Sebastiaan Heidt, Arend Mulder, Jan Voorberg, S. Marieke van Ham, Manfred Wuhrer, Anja ten Brinke, Gestur Vidarsson

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Immune-mediated platelet refractoriness (PR) remains a significant problem in the setting of platelet transfusion and is predominantly caused by the presence of alloantibodies directed against class I human leukocyte antigens (HLA). Opsonization of donor platelets with these alloantibodies can result in rapid clearance after transfusion via multiple mechanisms, including antibody dependent cellular phagocytosis (ADCP). Interestingly, not all alloimmunized patients develop PR to unmatched platelet transfusions, suggesting variation in HLA-specific IgG responses between patients. Previously, we observed that the glycosylation profile of anti-HLA antibodies was highly variable between PR patients, especially with respect to Fc galactosylation, sialylation and fucosylation. In the current study, we investigated the effect of different Fc glycosylation patterns, with known effects on complement deposition and FcγR binding, on phagocytosis of opsonized platelets by monocyte-derived human macrophages. We found that the phagocytosis of antibody- and complement-opsonized platelets, by monocyte derived M1 macrophages, was unaffected by these qualitative IgG-glycan differences.
Original languageEnglish
Article number2129604
Number of pages9
JournalPlatelets
Volume34
Issue number1
Early online date3 Oct 2022
DOIs
Publication statusPublished - 2023

Keywords

  • Alloimmunization
  • Blood Platelets/metabolism
  • Complement System Proteins/metabolism
  • Fc glycosylation
  • HLA Antigens
  • Humans
  • Immunoglobulin G
  • Isoantibodies
  • Macrophages
  • anti-HLA
  • phagocytosis
  • platelet transfusion

Cite this