Ho Yik C, Ahuja Kiran D K, Adams Murray J
1 School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia.
2 School of Veterinary and Life Sciences, Murdoch University, Murdoch, Western Australia, Australia.
Clin Appl Thromb Hemost. 2018 Oct;24(7):1128-1133. doi: 10.1177/1076029617736384. Epub 2017 Nov 9.
Anti-beta-2-glycoprotein 1 (anti-βGP1) antibodies are associated with increased thrombotic risk in patients with autoimmune disease. There is conflicting evidence on the effects of anti-βGP1 antibodies on platelets, with both enhanced and inhibited aggregation previously reported. However, previous studies did not include isotype antibodies to ensure the observed effects were due to anti-βGP1 antibodies. The aims of this study were to (1) investigate the effects of anti-βGP1 antibodies on collagen-induced platelet aggregation in parallel with negative control (buffer normal saline) and isotype control antibodies and (2) determine the lupus anticoagulant (LA) activity of anti-βGP1 antibodies used. Three animal-derived anti-human-βGP1 antibodies (1.25, 2.5, and 5 μg/mL) incubated with healthy platelet-rich plasma were activated by collagen (2.5 μg/mL). Each anti-βGP1 antibody demonstrated the inhibition of aggregation compared to negative control, but not to isotype control. No anti-βGP1 antibody demonstrated LA activity, suggesting they were probably nonpathological. This study highlights both negative and isotype control markers are important to validate the effects of anti-βGP1 antibodies. Assays to measure anti-domain I-βGP1 antibodies are recommended to be used in conjunction with functional measures to further investigate the effects of anti-βGP1 antibodies.
抗β2糖蛋白1（抗βGP1）抗体与自身免疫性疾病患者血栓形成风险增加有关。关于抗βGP1抗体对血小板的影响，存在相互矛盾的证据，此前有报道称其既有增强聚集的作用，也有抑制聚集的作用。然而，以往的研究并未纳入同型抗体以确保观察到的效应是由抗βGP1抗体所致。本研究的目的是：（1）将抗βGP1抗体与阴性对照（缓冲生理盐水）和同型对照抗体并行，研究其对胶原诱导的血小板聚集的影响；（2）测定所用抗βGP1抗体的狼疮抗凝物（LA）活性。将三种动物源性抗人βGP1抗体（1.25、2.5和5μg/mL）与健康富血小板血浆孵育后，用胶原（2.5μg/mL）激活。与阴性对照相比，每种抗βGP1抗体均表现出聚集抑制作用，但与同型对照相比则无此作用。没有抗βGP1抗体表现出LA活性，提示它们可能无致病性。本研究强调阴性对照和同型对照标志物对于验证抗βGP1抗体的效应均很重要。建议将检测抗I结构域βGP1抗体的试验与功能检测结合使用，以进一步研究抗βGP1抗体的效应。
