Pathogenic anti-β2-glycoprotein I antibodies recognize domain I of β2-glycoprotein I only after a conformational change
Pathogenic anti-β2-glycoprotein I antibodies recognize domain I of β2-glycoprotein I only after a conformational change
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DOI：
10.1182/blood-2005-05-1943
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发表时间：
2006-03-01
期刊：
影响因子：
20.3
通讯作者：
de Groot, PG
中科院分区：
文献类型：
--
作者：
de Laat, B;Derksen, RHWM;de Groot, PG
最近，我们发表了2个群体的抗β（2）-糖蛋白I（β（2）-GPI）IgG抗体的存在。A型抗体识别β（2）-GPI结构域I中的表位G40-R43，并与血栓形成强烈相关。B型抗体识别β 2-GPI的其他部分，与血栓形成无关。在这项研究中，我们证明，A型抗体只识别血浆纯化的β（2）-GPI时，涂布在带负电荷的表面上，而不是当涂布在中性电荷的表面上。B型抗体对血浆纯化的β（2）-GPI的亲和力与β 2-GPI包被的表面的电荷无关。A型抗体在溶液中不识别血浆纯化的β 2-GPI，而在溶液中和包被在中性电荷板上的重组β 2-GPI中，它们都识别。当从血浆纯化的β 2-GPI中去除碳水化合物链时，我们发现A型抗体确实识别溶液中的蛋白质。这支持了这样的假设：血浆纯化的和重组的β 2-GPI的识别差异是由糖基化的差异引起的，并且血浆纯化的β（2）-GPI的表位G40-R43被碳水化合物链覆盖。A型抗β（2）-GPI抗体仅在该碳水化合物链由于构象变化而被置换时才能识别该表位。这一发现对于致病性抗β 2-GPI抗体的检测和抗磷脂综合征病理生理学的理解具有重要意义。
Recently, we published the existence of 2 populations of anti-beta(2)-glycoprotein I (beta(2)-GPI) IgG antibodies. Type A antibodies recognize epitope G40-R43 in domain I of beta(2)-GPI and are strongly associated with thrombosis. Type B antibodies recognize other parts of beta(2)-GPI and are not associated with thrombosis. In this study we demonstrate that type A antibodies only recognize plasma-purified beta(2)-GPI when coated onto a negatively charged surface and not when coated onto a neutrally charged surface. The affinity of type B antibodies toward plasma-purified beta(2)-GPI was independent of the charge of the surface to which beta 2-GPI was coated. Type A antibodies did not recognize plasma-purified beta 2-GPI in solution, whereas they did recognize recombinant beta 2-GPI both in solution and coated onto a neutrally charged plate. When the carbohydrate chains were removed from plasma-purified beta 2-GPI, we found that type A antibodies did recognize the protein in solution. This supports the hypothesis that the difference in recognition of plasma-purified and recombinant beta 2-GPI is caused by the difference in glycosylation and that epitope G40-R43 of plasma-purified beta(2)-GPI is covered by a carbohydrate chain. Type A anti-beta(2)-GPI antibodies can only recognize this epitope when this carbohydrate chain is displaced as a result of a conformational change. This finding has major implications both for the detection of pathogenic anti-beta(2)-GPI antibodies and the comprehension of the pathophysiology of the antiphospholipid syndrome.