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Anti-laminin-1 Autoantibodies, Pregnancy Loss and Endometriosis

机译:抗Laminin-1自身抗体,妊娠减少和子宫内膜异位症

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Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, α1, β1 and γ1 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-α1, -β1 and -γ1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-α1, -β1 and -γ1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of α1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with –mouse— laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmune-mediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.
机译:层粘连蛋白-1是基底膜的主要成分和多功能糖蛋白,由三个不同的亚基α1,β1和γ1链组成。它是胚胎发生过程中最早合成的网络形成蛋白,在胚胎发育,胚胎着床和胎盘形成中起着重要作用。我们最近显示,IgG抗laminin-1抗体与复发的早孕流产和随后的妊娠结局显着相关。有趣的是,在患有子宫内膜异位症相关性不育的患者中也观察到了这些抗体,但在其他不育原因(包括输卵管因素,激素和子宫异常)的患者中未观察到这些抗体。在90%的子宫内膜异位病变中检测到层粘连蛋白-α1,-β1和-γ1mRNA,所有层粘连蛋白-α1,-β1和-γ1链均位于子宫内膜异位腹膜病变的腺上皮基底膜中。蛋白质印迹分析表明,这些患者的抗laminin-1抗体与所有laminin-1的链反应。 ELISA还证实了这些抗体的靶表位之一位于层粘连蛋白-1分子的特定区域,即α1链的羧基末端球状G结构域。我们最近建立的IgM单克隆抗Laminin-1自身抗体也识别G结构域。用–小鼠–层粘连蛋白-1免疫的小鼠产生的抗层粘连蛋白-1抗体可导致较高的胎儿吸收率,并具有较低的胚胎和胎盘重量。因此,抗laminin-1抗体在自身免疫介导的生殖衰竭的发展中可能很重要,对抗体的评估可能会提供一种新型的非侵入性子宫内膜异位诊断。

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