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Thromb Haemost
DOI: 10.1055/a-2787-0045
Original Article: Cellular Haemostasis and Platelets

Fc-dependent and -independent Platelet Clearance Caused by Anti-CD36 IgG1 and IgG2 Subclasses

Authors

  • Hui Ren  ‡   ‡

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Dawei Chen‡   ‡

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Yalin Luo‡   ‡

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Xiuzhang Xu

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Wenjie Xia

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Xin Ye

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Jiansen He

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Yaori Xu

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Jing Liu

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Shengxue Luo

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Huaqin Liang

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    2   The Key Medical Laboratory of Guangzhou, Guangzhou, China

  • Sentot Santoso

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    3   Institute for Clinical Immunology, Transfusion Medicine and Hemostasis, Justus-Liebig-University Giessen, Giessen, Germany

  • Yongshui Fu

    1   Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
    4   Department of Institute of Blood Transfusion and Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China
    5   Department of Transfusion Medicine, School of Medicine, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
    6   Center of Guangdong Precision Blood Transfusion Engineering Technology Research, Guangzhou, China

Funding Information This study was supported by National Natural Science Foundation of China (No. 82270237 and No. 82470231), Science and Technology Projects in Guangzhou (No. 20241A011068, No. 2025A03J3367, No. 2025A03J3369, No. 2025A03J3453, No. 2024A03J0375, and No.2024A03J0079), the Basic and Applied Basic Research Foundation of Guangdong (No. 2023A1515010924, No. 2025A1515010465, and No. 2024A1515012652), and the Key Medical Disciplines and Specialties Program of Guangzhou (2025–2027).
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Graphical Abstract

Abstract

Background

Anti-CD36 isoantibodies can induce platelet transfusion refractoriness and fetal neonatal immune thrombocytopenia. However, the mechanism of platelet clearance mediated by these antibodies (Abs) in such disorders remains unknown.

Objectives

We analyzed platelet clearance caused by mouse and human CD36 monoclonal Abs GZ1 IgG1 and IgG2 subclasses in vitro and in vivo.

Methods

Platelet clearance was evaluated in vitro by platelet phagocytosis assays and in vivo by monoclonal Ab GZ1 administration to C57BL/6J mice. Platelet activation, apoptosis, and desialylation were analyzed by flow cytometry.

Results

Both anti-CD36 Abs subclasses caused lower platelet clearance than anti-αIIbβ3 owing to the FcγR occupancy of monocytes by anti-CD36 Abs. This reaction could lead to mild thrombocytopenia, compared with the severe thrombocytopenia induced by anti-αIIbβ3 platelet-specific Abs. IgG subclass-mediated platelet clearance was inhibited by anti-FcγR Abs and intravenous immunoglobulin (IVIG). The human IgG2 Ab subclass caused lower platelet clearance than IgG1. IgG1- and IgG2-mediated platelet phagocytosis was inhibited by anti-FcγRI and anti-FcγRII, respectively. Unlike IgG1, the IgG2 Ab subclass induced platelet activation, apoptosis, and desialylation and platelet clearance by endothelial cells via Fc-independent pathway.

Conclusion

IgG1 and IgG2 subclasses of anti-CD36 Abs triggered platelet clearance primarily via the Fc-dependent pathway. The IgG2 Ab subclass, however, additionally induced platelet clearance via the Fc-independent pathway. These results indicate that the anti-CD36 Ab IgG subclass influences platelet clearance efficiency and may therefore determine the severity of immune thrombocytopenia caused by anti-CD36 antibodies.

Keywords

CD36 - platelet clearance - Fcγ receptor

‡ These authors contributed equally to this article.


Supplementary Material



Publication History

Received: 14 July 2025

Accepted after revision: 12 January 2026

Article published online:
29 January 2026

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