Pregnancy loss and endometriosis - Pathogenic role of anti-laminin-1 autoantibodies
Pregnancy loss and endometriosis - Pathogenic role of anti-laminin-1 autoantibodies
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DOI：
10.1196/annals.1361.059
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Matsuura, E
中科院分区：
文献类型：
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作者：
Inagaki, J;Kondo, A;Matsuura, E
Laminin-1 是一种主要的多功能糖蛋白，形成基底膜支架网络的组成部分，并且是胚胎发生过程中最早合成的成分。这种蛋白质（α1β1γ1）在胚胎发育过程中的基底膜组装和外胚层分化中发挥着重要作用。已知抗层粘连蛋白-1 自身抗体会导致动物不育和反复自然流产。最近，我们报道了血液中 IgG 抗层粘连蛋白 1 抗体 (Abs) 的存在与妊娠早期反复流产和随后的阴性妊娠结局显着相关。有趣的是，这些抗体也与不孕症，尤其是子宫内膜异位症引起的不孕症密切相关。在 90% 的子宫内膜异位病变中也检测到层粘连蛋白-α 1、层粘连蛋白-β 1 和层粘连蛋白-γ 1 mRNA，并且所有层粘连蛋白-α 1、层粘连蛋白-β 1 和层粘连蛋白-γ 1 链都定位于子宫内膜异位性腹膜病变中腺上皮的基底膜。 ELISA 显示自身抗体对层粘连蛋白-1 分子的特定区域（即 α1 链 G 结构域）具有特异性反应性。我们最近建立的IgM单克隆抗层粘连蛋白-1抗体也识别G结构域并与位于人子宫内膜腺上皮基底膜的人α1链发生交叉反应。我们还建立了一个动物模型，在用小鼠 laminin-1 免疫后产生高滴度的抗 laminin-1 抗体。免疫小鼠的抗层粘连蛋白 1 抗体导致胎儿吸收率较高，胚胎和胎盘重量较低。因此，抗层粘连蛋白-1 抗体可能在自身免疫介导的生殖失败的发展中很重要，并且对此类抗体的评估可能为子宫内膜异位症的无创诊断提供新的手段。
Laminin-1 is a major multifunctional glycoprotein that forms an integral part of the scaffolding network of basement membranes, and is the earliest synthesized component during embryogenesis. This protein (alpha 1 beta 1 gamma 1) plays an important role in basement membrane assembly and epiblast differentiation during embryonic development. Anti-laminin-1 autoantibodies are known to cause infertility and recurrent spontaneous abortion in animals. Recently, we reported that the presence of IgG anti-laminin-1 antibodies (Abs) in the blood is significantly associated with recurrent first-trimester miscarriages and subsequent negative pregnancy outcomes. Interestingly, these antibodies are also strongly associated with infertility, especially infertility caused by endometriosis. Laminin-alpha 1, laminin-beta 1, and laminin-gamma 1 mRNAs were also detected in 90% of endometriotic lesions, and all laminin-alpha 1, laminin-beta 1, and laminin-gamma 1 chains were localized to the basement membranes of glandular epithelium in endometriotic peritoneal lesions. ELISA showed specific reactivity of the autoantibodies to a particular region of the laminin-1 molecule, that is, the alpha 1 chain G domain. IgM monoclonal anti-laminin-1 Abs, which we recently established, also recognized the G domain and cross-reacted with human alpha 1 chain located in the basement membrane of the glandular epithelium of human endometrium. We also established an animal model that produced high titers of anti-laminin-1 Abs after immunization with mouse laminin-1. Anti-laminin-1 Abs from the immunized mice caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 Abs may be important in the development of autoimmune-mediated reproductive failures, and the assessment of the such antibodies may provide a novel means for noninvasive diagnosis of endometriosis.