Christopoulos C
Department of Haematology, University College Hospital, London, UK.
Clin Exp Immunol. 1994 Oct;98(1):6-11. doi: 10.1111/j.1365-2249.1994.tb06598.x.
Platelet surface immunoglobulin G (PSIgG) was measured ex vivo in nine patients with stable angina pectoris receiving continuous (48-96 h) infusions of Fab fragments of a chimaeric MoAb (human IgG with murine variable regions) to platelet glycoprotein IIb-IIIa. PSIgG was measured using flow cytometry (FC) and an Fc-specific anti-IgG polyclonal antibody, which did not cross-react with the chimaeric Fab fragment (c7E3-Fab). A variable but statistically significant (P < 0.05) elevation of PSIgG was present within 24 h after the onset of the infusion, and was more marked (P < 0.01) several days after the end of the infusion despite an exponential fall in platelet surface c7E3-Fab post-infusion. PSIgG returned to normal within 2 weeks after the end of the infusion. The timing of IgG recruitment to the platelet surface suggested the pre-existence in the patients' plasma of IgG binding to c7E3-Fab-bearing platelets. None of the patients developed thrombocytopenia. In order to assess the incidence of IgG bindable to c7E3-Fab-bearing platelets in controls clinically comparable to the c7E3-Fab infusion patients, normal platelets coated with either chimaeric (c) or murine (m) 7E3-Fab were incubated with plasmas from 21 patients with ischaemic heart disease, and recruitment of IgG to the platelet surface was measured by FC. Fourteen of the 21 plasmas contained IgG bindable to c7E3-Fab-coated platelets, whereas only one of the 21 plasmas contained IgG bindable to m7E3-Fab-coated platelets (a highly significant difference, P < 0.001). These findings indicate that infusions of Fab fragments of the chimaeric anti-platelet antibody 7E3 are often associated with elevations in PSIgG, which are probably due to pre-existing 'naturally occurring' antibodies to the Fab fragments of chimaeric (but not murine) 7E3, and most probably other chimaeric MoAbs. The possible clinical significance of such ex vivo measured activities is at present a matter for speculation, and requires further study.
在9例稳定型心绞痛患者中，对其进行持续（48 - 96小时）输注针对血小板糖蛋白IIb - IIIa的嵌合单克隆抗体（具有鼠可变区的人IgG）的Fab片段后，离体测量血小板表面免疫球蛋白G（PSIgG）。使用流式细胞术（FC）和一种不与嵌合Fab片段（c7E3 - Fab）发生交叉反应的Fc特异性抗IgG多克隆抗体来测量PSIgG。输注开始后24小时内，PSIgG出现了可变但具有统计学意义（P < 0.05）的升高，尽管输注后血小板表面c7E3 - Fab呈指数下降，但在输注结束几天后升高更为明显（P < 0.01）。输注结束后2周内，PSIgG恢复正常。IgG募集到血小板表面的时间表明患者血浆中预先存在与携带c7E3 - Fab的血小板结合的IgG。所有患者均未发生血小板减少症。为了评估在临床上与c7E3 - Fab输注患者可比的对照组中可与携带c7E3 - Fab的血小板结合的IgG的发生率，将包被有嵌合（c）或鼠源（m）7E3 - Fab的正常血小板与21例缺血性心脏病患者的血浆一起孵育，并通过FC测量IgG募集到血小板表面的情况。21份血浆中有14份含有可与包被c7E3 - Fab的血小板结合的IgG，而21份血浆中只有1份含有可与包被m7E3 - Fab的血小板结合的IgG（差异极显著，P < 0.001）。这些发现表明，嵌合抗血小板抗体7E3的Fab片段输注常与PSIgG升高相关，这可能是由于预先存在针对嵌合（而非鼠源）7E3的Fab片段以及很可能其他嵌合单克隆抗体的“天然存在”抗体所致。这种离体测量活性的可能临床意义目前尚属推测，需要进一步研究。
