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Mechanisms of disease: antiphospholipid antibodies-from clinical association to pathologic mechanism.

机译:疾病机制:抗磷脂抗体-从临床关联到病理机制。

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The discovery that antiphospholipid antibodies recognize plasma proteins that bind to phospholipids rather than recognizing phospholipids themselves has been a major advance in research into antiphospholipid syndrome (APS). It is now established that beta2-glycoprotein I (beta2 GPI) is the most important antigen for antiphospholipid antibodies. However, the possible pathologic mechanism is still much debated. This is mainly because not all patients with anti-beta2 GPI antibodies show clinical symptoms that are related to APS. Several reports indicate that anti-beta2 GPI antibodies with lupus anticoagulant (LA) activity are clinically of much importance. Most patients with LA caused by anti-beta2 GPI antibodies suffer from thrombosis as a result of recognition of the first domain of beta2 GPI by these antibodies. In the search for a pathologic mechanism that might explain the high occurrence of thrombosis in patients with anti-domain I antibodies (LA-causing anti-beta2 GPI antibodies), it was found thatthese antibodies show increased resistance to the anticoagulant activity of annexin A5. We have shown that the same population of antibodies also displays increased resistance to activated protein C. Owing to the diversity of clinical symptoms related to APS, it is likely that other pathologic mechanisms also contribute to the occurrence of APS-related symptoms.
机译:抗磷脂抗体识别与磷脂结合的血浆蛋白而不是识别磷脂本身的发现是抗磷脂综合征(APS)研究的一项重大进展。现在已经确定,β2-糖蛋白I(β2GPI)是抗磷脂抗体最重要的抗原。但是,可能的病理机制仍存在很多争议。这主要是因为并非所有具有抗beta2 GPI抗体的患者都显示出与APS相关的临床症状。几篇报道表明,具有狼疮抗凝(LA)活性的抗β2GPI抗体在临床上非常重要。由抗β2GPI抗体引起的大多数LA患者由于这些抗体识别β2GPI的第一个结构域而遭受血栓形成。在寻找可能解释具有抗结构域I抗体(LA引起的抗β2GPI抗体)的患者血栓形成高发的病理机制中,发现这些抗体对膜联蛋白A5的抗凝血活性显示出更高的抗性。我们已经显示相同的抗体群体也显示出对活化蛋白C的增加的抵抗力。由于与APS相关的临床症状的多样性,其他病理机制也可能也导致了APS相关症状的发生。

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