TY - JOUR
T1 - Phagocytosis of platelets opsonized with differently glycosylated anti-HLA hIgG1 by monocyte-derived macrophages
AU - van Osch, Thijs L. J.
AU - Steuten, Juulke
AU - Nouta, Jan
AU - Koeleman, Carolien A. M.
AU - Bentlage, Arthur E. H.
AU - Heidt, Sebastiaan
AU - Mulder, Arend
AU - Voorberg, Jan
AU - van Ham, S. Marieke
AU - Wuhrer, Manfred
AU - ten Brinke, Anja
AU - Vidarsson, Gestur
N1 - Funding Information:
This work was supported by Stichting Sanquin Bloedvoorziening (PPO 17-44). The authors would like to thank Rick Kapur, Leendert Porcelijn, C. Ellen van der Schoot and Masja de Haas for constructive feedback during discussions and the Sanquin Research Central Facility for their technical assistance with conventional and imaging flow cytometry.
Publisher Copyright:
© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Alloimmunization
KW - Fc glycosylation
KW - anti-HLA
KW - phagocytosis
KW - platelet transfusion
UR - https://www.scopus.com/pages/publications/85139181418
U2 - 10.1080/09537104.2022.2129604
DO - 10.1080/09537104.2022.2129604
M3 - Article
C2 - 36185007
SN - 0953-7104
VL - 34
JO - Platelets
JF - Platelets
IS - 1
M1 - 2129604
ER -