产科抗磷脂综合征的表观遗传学研究进展

Epigenetic research progress in obstetric antiphospholipid syndrome

产科抗磷脂综合征(APS)是一种系统性自身免疫性疾病,临床以早期复发性流产、早产、死胎、胎盘功能不全、子痫前期等病理妊娠为主要表现,主要病因是抗磷脂抗体持续阳性引发的动静脉血栓形成和免疫炎症反应。目前关于产科APS的研究多集中在实验室检测和临床特点上,缺少对其确切发病机制的深入探讨。众所周知,中性粒细胞、单核细胞、内皮细胞、血小板、滋养细胞的功能障碍是产科APS发生、发展的关键因素,近年来研究显示这些细胞的表观遗传学改变(主要包括DNA甲基化、组蛋白修饰、非编码RNA)涉及产科APS发病中免疫炎症反应、血栓形成和病理妊娠的基因表达和沉默。鉴于表观遗传学标志物作为产科APS诊断性标志物或治疗靶点的潜力,本文就产科APS发生、发展的表观遗传学机制作一综述。

Obstetric antiphospholipid syndrome(APS)is a systematic autoimmune disease accompanied,which is clinically characterized by early recurrent abortion,premature delivery,stillbirth,placental insufficiency and preeclampsia etc.The main etiology is arteriovenous thrombosis and immune inflammatory response caused by continuous positive antiphospholipid antibodies.Nowadays,most researches focus on the laboratory detection and clinic features of obstetric APS,but its precise etiology remains to be deeply explored.As we all know,the dysfunction of neutrophils,monocytes,endothelial cells,platelets,trophoblasts are key contributors to obstetric APS progression.Recent studies have shown that their epigenetic variations,mainly including the DNA methylation,histone modifications and non-coding RNAs,result in genes expression or silence engaged in immune inflammatory response,thrombosis formation and morbid pregnancy in obstetric APS.Given the potential of epigenetic markers serving as diagnostic biomarkers or therapeutic targets of obstetric APS,the epigenetic mechanisms of the occurrence and development of obstetric APS were mainly reviewed in this paper.