CD36单克隆抗体体内清除血小板的机制探讨*

doi:10.3969/j.issn.1671-2587.2025.01.006

临床输血与检验 ›› 2025, Vol. 27 ›› Issue (1): 48-53.DOI: 10.3969/j.issn.1671-2587.2025.01.006

CD36单克隆抗体体内清除血小板的机制探讨^*

徐秀章, 陈大伟, 夏文杰, 邓晶, 陈扬凯, 丁浩强, 刘静, 叶欣

广州市血液安全重点实验室,广州血液中心广州 510095

收稿日期:2024-06-12 发布日期:2025-02-25
通讯作者: 叶欣,主要从事输血遗传免疫学研究,（E-mail）779684055@qq.com。
作者简介:徐秀章,主要从事输血医学相关工作,（E-mail）497997452@qq.com。
基金资助:
*本课题受广东省自然科学基金（No.2024A1515012652）、广州市科技计划项目（No.202201011749、No.2024A03J0375、No.2023A03J0549、No.2023A03J0552、No.202201010013、No.2023A03J0997、No.2025A03J3369）资助

The Study on the Mechanism of Platelet Clearance Caused by Anti-CD36 Monoclonal Antibodies in Vivo

XU Xiuzhang, CHEN Dawei, XIA Wenjie, DENG Jing, CHEN Yangkai, DING Haoqiang, LIU Jing, YE Xin

The Key Medical Laboratory of Guangzhou, Guangzhou Blood Center, Guangzhou 510095

Received:2024-06-12 Published:2025-02-25

摘要/Abstract

摘要： 目的探讨CD36抗体在体内介导血小板吞噬清除的作用机制。方法将单克隆抗体（mAb）32-106（IgG2a）以2 mg/kg的浓度注射给C57BL/6J雌鼠,并分别在注射前0 h、注射后0.5 h、1 h、2 h、4 h、6 h及24 h检测小鼠体内血小板数量,通过胃蛋白酶消化处理,获得32-106的F（ab'）₂段,并将其注射给C57BL/6J雌鼠,分析其清除CD36（+）血小板的效果,制备其他亚型的32-106,通过体内实验分析其对CD36（+）血小板的清除作用。结果体内实验证实,mAb 32-106 IgG2a可导致C57BL/6J雌鼠体内血小板数的明显降低（P<0.05）,而mAb 32-106的F（ab'）₂段并不引起雌鼠体内血小板的减少。C57BL/6J雌鼠接受2 mg/kg的32-106 IgG1或32-106 IgG3,也发生血小板数量降低,但与32-106 IgG2a相比,IgG1及IgG3亚型32-106引起的小鼠血小板减少不明显。结论通过体内实验证实,CD36抗体以Fc依赖途径参与体内CD36（+）血小板的清除,且IgG2a亚型的抗体引起的血小板清除效果显著。

关键词: CD36, 单克隆抗体, 血小板清除, Fc依赖

Abstract: Objective To study the mechanism of platelet clearance caused by anti-CD36 antibodies in vivo. Methods The monoclonal antibody (mAb) 32-106 (IgG2a) was injected into the C57BL/6J female mice at a concentration of 2 mg/kg, and the platelet counts of these mice were detected at 0 h before injection, 0.5 h, 1 h, 2 h, 4 h, 6 h and 24 h after injection. The F (ab') 2 segment of 32-106 was obtained by digestion with pepsin and then injected into the C57BL/6J mice to analyze its clearance effect on CD36 (+) platelets. Subsequently, other subclasses of mAb 32-106 were generated and injected into the mice to analyze its clearance effect on CD36 (+) platelets. Results mAb 32-106 IgG2a significantly decreased the number of CD36 (+) platelets in C57BL/6J female mice (P<0.05) in vivo. However, the F (ab') ₂ segment of mAb 32-106 did not cause platelet clearance in female mice. The C57BL/6J female mice receiving 2 mg/kg of 32-106 IgG1 or 32-106 IgG3 also experienced decreased platelet counts. Compared with 32-106 IgG2a, the thrombocytopenia induced by 32-106 IgG3 or 32-106 IgG1 was not significant in mice. Conclusion The clearance of CD36 (+) platelets caused by anti-CD36 antibodies in vivo is in an Fc-dependent pathway, and anti-CD36 IgG2a antibody has a significant effect on CD36 (+) platelet clearance.

Key words: CD36, Monoclonal antibody, Platelet clearance, Fc-dependent

中图分类号:

R457

徐秀章, 陈大伟, 夏文杰, 邓晶, 陈扬凯, 丁浩强, 刘静, 叶欣. CD36单克隆抗体体内清除血小板的机制探讨^*[J]. 临床输血与检验, 2025, 27(1): 48-53.

XU Xiuzhang, CHEN Dawei, XIA Wenjie, DENG Jing, CHEN Yangkai, DING Haoqiang, LIU Jing, YE Xin. The Study on the Mechanism of Platelet Clearance Caused by Anti-CD36 Monoclonal Antibodies in Vivo[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(1): 48-53.

参考文献

[1] YANG M A,SILVERSTEIN R L.CD36 signaling in vascular redox stress[J].Free Radic Biol Med,2019,136:159-171.
[2] FEBBRAIO M,HAJJAR D P,SILVERSTEIN R L.CD36:a class B scavenger receptor involved in angiogenesis,atherosclerosis,inflammation,and lipid metabolism[J].J Clin Invest,2001,108(6):785-791.
[3] LIU Q R,LIU J Y,ZHAO J Y,et al.Do anti-CD36 antibodies cause only fetal/neonatal alloimmune thrombocytopenia?[J].Br J Haematol,2023,202(6):e62-e66.
[4] SCHMIDT A E,SAHAI T,REFAAI M A,et al.Severe platelet transfusion refractoriness in association with antibodies against CD36[J].Lab Med,2020,51(5):540-544.
[5] BIERLING P,GODEAU B,FROMONT P,et al.Posttransfusion Purpura-like syndrome associated with CD36(Naka)isoimmunization[J].Transfusion,1995,35(9):777-782.
[6] XU X Z,YE X,XIA W J,et al.Studies on CD36 deficiency in South China:two cases demonstrating the clinical impact of anti-CD36 antibodies[J].Thromb Haemost,2013,110(6):1199-1206.
[7] KHATRI S S,CURTIS B R,YAMADA C.A case of platelet transfusion refractoriness due to anti-CD36 with a successful treatment outcome[J].Immunohematology,2019,35(4):139-144.
[8] SCHMIDT A E,SAHAI T,REFAAI M A,et al.Severe platelet transfusion refractoriness in association with antibodies against CD36[J].Lab Med,2020,51(5):540-544.
[9] PEDINI P,HICHERI Y,BERTAND G,et al.A case of platelet transfusion refractoriness in a CD36-negative patient with acute myeloid leukemia:diagnostic and therapeutic management[J].Transfusion,2022,62(10):2148-2150.
[10] XU X Z,LI L,XIA W J,et al.Successful management of a hydropic fetus with severe Anemia and thrombocytopenia caused by anti-CD36 antibody[J].Int J Hematol,2018,107(2):251-256.
[11] XIA W,YE X,XU X,et al.Two cases of platelet transfusion refractoriness and one case of possible FNAIT caused by antibodies against CD36 in China[J].Transfus Med,2014,24(4):254-256.
[12] WU G G,ZHOU Y,LI L L,et al.Platelet immunology in China:research and clinical applications[J].Transfus Med Rev,2017,31(2):118-125.
[13] 周燕,李丽兰,钟周琳,等.造血干细胞移植术后抗-CD36抗体介导的血小板输注无效症和相关病例的实验研究[J].中国实验血液学杂志,2018,26(2):541-546.
[14] NIESWANDT B,BERGMEIER W,RACKEBRANDT K,et al.Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic Purpura in mice[J].Blood,2000,96(7):2520-2527.
[15] LI C L,PIRAN S,CHEN P G,et al.The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies[J].J Clin Invest,2011,121(11):4537-4547.
[16] XU X Z,CHEN D W,YE X,et al.Successful prenatal therapy for anti-CD36-mediated severe FNAIT by deglycosylated antibodies in a novel murine model[J].Blood,2021,138(18):1757-1767.
[17] LI J E,VAN DER WAL D E,ZHU L Y,et al.Fc-independent phagocytosis:implications for IVIG and other therapies in immune-mediated thrombocytopenia[J].Cardiovasc Hematol Disord Drug Targets,2013,13(1):50-58.
[18] CHEN D W,KANG T,XU X Z,et al.Mechanism and intervention of murine transfusion-related acute lung injury caused by anti-CD36 antibodies[J].JCI Insight,2023,8(6):e165142.
[19] KUIJPERS M J,VAN DER MEIJDEN P E,FEIJGE M A,et al.Factor XII regulates the pathological process of Thrombus formation on ruptured plaques[J].Arterioscler Thromb Vasc Biol,2014,34(8):1674-1680.
[20] ZEILER M,MOSER M,MANN M.Copy number analysis of the murine platelet proteome spanning the complete abundance range[J].Mol Cell Proteomics,2014,13(12):3435-3445.
[21] TEMMING A R,BENTLAGE A E H,DE TAEYE S W,et al.Cross-reactivity of mouse IgG subclasses to human fc gamma receptors:antibody deglycosylation only eliminates IgG2b binding[J].Mol Immunol,2020,127:79-86.
[22] NI H Y,CHEN P G,SPRING C M,et al.A novel murine model of fetal and neonatal alloimmune thrombocytopenia:response to intravenous IgG therapy[J].Blood,2006,107(7):2976-2983.
[23] WEBSTER M L,SAYEH E,CROW M,et al.Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIbalpha antibodies[J].Blood,2006,108(3):943-946.

CD36单克隆抗体体内清除血小板的机制探讨^*

The Study on the Mechanism of Platelet Clearance Caused by Anti-CD36 Monoclonal Antibodies in Vivo

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