Pathogenic role of anti-beta2-glycoprotein I antibodies on human placenta: functional effects related to implantation and roles of heparin.
Pathogenic role of anti-beta2-glycoprotein I antibodies on human placenta: functional effects related to implantation and roles of heparin.
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抗 β2-糖蛋白 I 抗体对人胎盘的致病作用：与植入相关的功能效应和肝素的作用。
DOI：
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发表时间：
2007
影响因子：
13.3
通讯作者：
Alessandro Caruso
中科院分区：
文献类型：
--
作者：
N. Simone;P. Meroni;M. D’Asta;F. Nicuolo;M. D'alessio;Alessandro Caruso
抗磷脂综合征（APS）的大多数临床表现可能与血栓形成事件有关;然而，胎盘血栓形成不能解释患有该综合征的女性发生的所有妊娠并发症。在这方面，已经假设抗磷脂（aPL）抗体可以直接攻击滋养层，但是仍然不清楚什么致病机制起作用以及涉及哪些aPL抗体亚群。尽管已经假定aPL抗体针对阴离子磷脂（PL），但本领域的当前进展表明，PL结合血浆蛋白如β 2-糖蛋白-I（β 2-GPI）的抗体是临床相关的aPL抗体。似乎在β 2-GPI与PL连接后，两种分子都经历构象变化，导致β 2-GPI结构内的隐蔽表位暴露，从而允许随后的抗体结合。通过抗β 2-GPI测定检测的aPL抗体与胎儿丢失相关。然而，关于抗体如何引起产科表现仍存在争议。妊娠期肝素治疗的显著改善的结果激发了人们对药物作用机制的兴趣。几种机制可以解释其有益作用，因为除了肝素对凝血级联的直接作用外，它还可以通过减少aPL抗体的结合、减少炎症、促进着床和/或抑制补体激活来保护妊娠。需要进一步的调查，以更好地了解aPL抗体如何诱导产科并发症，并更好地澄清肝素在人胎盘中的功能作用，从而获得更成功的治疗选择。
Most of the clinical manifestations of the antiphospholipid syndrome (APS) can be related to thrombotic events; however, placental thrombosis cannot explain all of the pregnancy complications that occur in women with this syndrome. In this regard, it has been hypothesized that antiphospholipid (aPL) antibodies can directly attack trophoblasts, but it is still unclear what pathogenetic mechanisms play a role and which aPL antibodies subpopulations are involved. Although it has been assumed that aPL antibodies are directed against anionic phospholipids (PLs), current advances in the field suggest that antibodies to PL-binding plasma protein such as beta2-glycoprotein-I (beta2-GPI) are the clinically relevant aPL antibodies. It appears that following the attachment of beta2-GPI to PLs, both molecules undergo conformational changes that result in the exposure of cryptic epitopes within the structure of beta2-GPI allowing the subsequent binding of antibodies. aPL antibodies detected by anti-beta2-GPI assays are associated with fetal loss. However, there is still debate on how the antibodies might induce the obstetrical manifestations. The significantly improved outcome of pregnancies treated with heparin has stimulated interest in the drug's mechanisms of action. Several mechanisms could explain its beneficial effects, because in addition to a direct effect of heparin on the coagulation cascade, it might protect pregnancies by reducing the binding of aPL antibodies, reducing inflammation, facilitating implantation and/or inhibiting complement activation. Further investigations are needed to better understand how aPL antibodies induce obstetric complications and to better clarify the functional role of heparin in the human placenta leading to more successful therapeutic options.
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影响因子：
158.5
作者：
Rand, JH;Wu, XX;Harpel, PC
通讯作者：
Harpel, PC
影响因子：
20.3
作者：
T. Mollnes;O. Brekke;M. Fung;H. Fure;D. Christiansen;G. Bergseth;V. Videm;K. Lappegård;J. Köhl;John D Lambris
通讯作者：
T. Mollnes;O. Brekke;M. Fung;H. Fure;D. Christiansen;G. Bergseth;V. Videm;K. Lappegård;J. Köhl;John D Lambris
影响因子：
20.1
作者：
FRIEDRICHS, GS;KILGORE, KS;LUCCHESI, BR
通讯作者：
LUCCHESI, BR
肝素的抗炎作用需要氨基葡萄糖 6-O-硫酸化，并通过 L-和 P-选择素的阻断介导。
DOI：
10.1172/jci14996
发表时间：
2002
期刊：
The Journal of clinical investigation.
影响因子：
--
作者：
Wang,Lianchun;Brown,JillianR;Varki,Ajit;Esko,JeffreyD
通讯作者：
Esko,JeffreyD
影响因子：
15.9
作者：
Girardi, G;Berman, J;Salmon, JE
通讯作者：
Salmon, JE