Immunology of preeclampsia
Immunology of preeclampsia
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DOI：
10.1159/000087912
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Sharma, S
中科院分区：
文献类型：
--
作者：
Matthiesen, L;Berg, G;Sharma, S
先兆子痫是一种胎盘依赖性疾病，具有局部和全身异常，新生儿和孕产妇发病率。它在怀孕后期表现出来，但发病是在怀孕早期阶段。目前关于先兆子痫病因学的假说主要集中在免疫反应的适应不良和滋养细胞侵袭缺陷上。因此，过度的母体炎症反应，可能是针对外源性胎儿抗原，导致一系列事件，包括浅滋养层侵入、螺旋动脉重塑缺陷、胎盘梗死和促炎细胞因子和胎盘碎片在体循环中的释放。在正常妊娠期间，滋养层细胞在蜕膜中与独特的子宫NK细胞相互作用，修改其细胞因子库，调节粘附分子和基质金属蛋白酶。滋养层细胞不能完成这些变化可能是先兆子痫发病的关键因素。在母胎界面产生的几种细胞因子对滋养层侵袭有影响。这表明，白细胞介素-10的缺乏可能有助于增强对滋养层引起的炎症反应，如肿瘤坏死因子-a和干扰素-γ。因此，受到高凋亡率的滋养层的侵入能力受到阻碍，导致螺旋动脉的转化缺陷、缺氧、血栓形成和胎盘梗塞。随后的胎盘梗塞导致母体循环中胎盘碎片和细胞因子的量增加的泄漏以及在先兆子痫中鉴定的过度的全身性内皮活化。到目前为止，先兆子痫的治疗主要集中在高血压等症状上，而改变免疫反应的尝试可能在未来成为可能。
Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental frag-ments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhe-sion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by eg tumour necrosis factor-a and interferon-y. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.