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

doi:10.1080/09537104.2022.2129604

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Article number	2129604
Pages (from-to)	1-9
Journal	Platelets
Volume	34
Issue number	1
DOIs	https://doi.org/10.1080/09537104.2022.2129604
Publication status	Published - Jan 2023

Bibliographical note

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.

Funding

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.

Keywords

Alloimmunization
anti-HLA
Fc glycosylation
phagocytosis
platelet transfusion

Access to Document

10.1080/09537104.2022.2129604Licence: CC BY-NC

Phagocytosis of platelets opsonized with differently glycosylated anti HLA hIgG1 by monocyte derived macrophagesFinal published version, 3.14 MBLicence: CC BY-NC

Cite this

van Osch, T. L. J., Steuten, J., Nouta, J., Koeleman, C. A. M., Bentlage, A. E. H., Heidt, S., Mulder, A., Voorberg, J., van Ham, S. M., Wuhrer, M., ten Brinke, A., & Vidarsson, G. (2023). Phagocytosis of platelets opsonized with differently glycosylated anti-HLA hIgG1 by monocyte-derived macrophages. Platelets, 34(1), 1-9. Article 2129604. https://doi.org/10.1080/09537104.2022.2129604

@article{51ab1d1d1a484c84b6745ba603b0c3db,

title = "Phagocytosis of platelets opsonized with differently glycosylated anti-HLA hIgG1 by monocyte-derived macrophages",

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.",

keywords = "Alloimmunization, anti-HLA, Fc glycosylation, phagocytosis, platelet transfusion",

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

note = "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: {\textcopyright} 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.",

year = "2023",

month = jan,

doi = "10.1080/09537104.2022.2129604",

language = "English",

volume = "34",

pages = "1--9",

journal = "Platelets",

issn = "0953-7104",

publisher = "Informa Healthcare",

number = "1",

}

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 - 2023/1

Y1 - 2023/1

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 - anti-HLA

KW - Fc glycosylation

KW - phagocytosis

KW - platelet transfusion

UR - http://www.scopus.com/inward/record.url?scp=85139181418&partnerID=8YFLogxK

U2 - 10.1080/09537104.2022.2129604

DO - 10.1080/09537104.2022.2129604

M3 - Article

C2 - 36185007

AN - SCOPUS:85139181418

SN - 0953-7104

VL - 34

SP - 1

EP - 9

JO - Platelets

JF - Platelets

IS - 1

M1 - 2129604

ER -

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

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this