[Roles of IgG1 and IgG2a subtypes in anti-glycoprotein Ⅰbα antibody-induced platelet clearance]

[IgG1 和 IgG2a 亚型在抗糖蛋白Ⅰbα抗体诱导的血小板清除中的作用]

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Abstract

OBJECTIVE: To investigate the role of the IgG subtypes(IgG1 and IgG2a)in anti-glycoprotein(GP)Ⅰbα antibody-induced platelet clearance. METHODS: Venous blood was collected from healthy volunteers, and platelets were separated. The phagocytosis of human platelets by human acute monocytic leukemia cells(THP-1 cells)induced by different anti-GPⅠbα antibodies(AN51, AK2, HIP1, TM60, VM16d, WM23, and SZ2)was detected by flow cytometry. The effects of the AN51 full-length antibody, F(ab')(2), and Fab fragments on platelet phagocytosis by THP-1 cells were detected by flow cytometry. Then, the Fc blocking antibody 2.4G2 and normal rat IgG2a or IgG1 were injected into C57BL/6J mice via the posterior ocular vein, and their effects on platelet reduction induced by R300 were detected by a hematology analyzer. RESULTS: Compared with IgG1, the IgG2a subtype of anti-GPⅠbα antibodies induced the phagocytosis of platelets by THP-1 cells in vitro(P<0.05). In contrast to the AN51 full-length antibody, neither AN51 F(ab')(2) nor the Fab fragment could induce THP-1 cells to phagocytose platelets(P<0.05). Compared with the control group, anti-mouse GPⅠbα R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of Fc blocking antibody 2.4G2(P<0.05). Similarly, R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of rat IgG2a(P<0.05). CONCLUSION: IgG2a plays an important role in anti-GPⅠbα-induced clearance.

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