目的:本综述旨在确定抗磷脂综合征(APS)患者血栓和/或产科事件复发风险的生物学标志物。
方法:对文献进行了全面回顾,以评估已建立的和潜在的与APS血栓形成相关的新型生物学标志物。为此,在过去的二十年中,使用以下关键字或其组合进行了PubMed文献检索:血栓形成风险,血栓复发,风险分层,严重程度,预测值。
结果:抗磷脂抗体(aPL)的N-糖基化分析显示,低水平的IgG唾液酸化,岩藻糖基化或半乳糖基化增加aPL的促炎活性,易患血栓形成.此外,对血清中中性粒细胞胞外陷阱(NETs)和针对NETs的抗体(抗-NETs)进行定量,证明在评估APS严重程度方面具有良好的预后价值.氧化应激在APS的致病性中起作用,对氧磷酶1(PON1)活性成为APS血栓形成风险的有希望的生物标志物。此外,鉴定与APS病理生理学有关的新抗原靶标,如溶异双磷脂酸(LBPA),导致了非常规aPL的发现,针对LBPA(aLBPA)的抗体,其临床价值可以识别血栓复发高风险的APS患者。
结论:aPL的免疫学特征,aPL的N-糖基化,NETs和反NETs的量化,氧化应激生物标志物的分析和aLBPA的发现为APS患者的危险分层提供了潜在的预后工具.
OBJECTIVE: This
review aims to identify biological markers associated with the risk of recurrence of thrombotic and/or obstetric events in patients with antiphospholipid syndrome (APS).
METHODS: A comprehensive
review of literature was conducted to evaluate established and potential novel biological markers associated with thrombosis in APS. To this end, a PubMed literature search was conducted for the last twenty years using the following keywords or their combinations: thrombotic risk, recurrence of thrombosis, risk stratification, severity, predictive value.
RESULTS: Previous studies showed that multiple aPL positivity correlates with an increased risk of thrombosis in APS. Moreover, the analysis of N-glycosylation of antiphospholipid antibodies (aPL) revealed that low levels of IgG sialylation, fucosylation or galactosylation increases the pro-inflammatory activity of aPL, predisposing to thrombosis. In addition, quantification of neutrophil extracellular traps (NETs) and antibodies directed against NETs (anti-NETs) in serum demonstrates promising prognostic utility in assessing APS severity. Oxidative stress plays a role in the pathogenicity of APS and paraoxonase 1 (PON1) activity emerges as a promising biomarker of thrombotic risk in APS. Furthermore, identification of novel antigenic targets involved in the pathophysiology of APS, such as lysobisphosphatidic acid (LBPA), had led to the discovery of unconventional aPL, antibodies directed against the LBPA (aLBPA), whose clinical value could make it possible to identify APS patients at high risk of thrombotic recurrence.
CONCLUSIONS: The immunological profile of aPL, N-glycosylation of aPL, quantification of NETs and anti-NETs, analysis of biomarkers of oxidative stress and the discovery of aLBPA offer potential prognostic tools for risk stratification in APS patients.