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Study of anti-laminin-1 autoantibodies in endometriosis-associated infertility

抗层粘连蛋白-1自身抗体在子宫内膜异位症相关不孕症中的研究

基本信息

批准号：
17591738
负责人：
INAGAKI Junko
金额：
$ 2.24万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

1. Anti-laminin-1 autoantibodies in infertile patients with endometriosis recognized N-linked oligosaccharide chains of mouse laminin-1. A percentage of patients expressed a natural antibody that recognizes the a-Gal (Galal- 3Ga1β1-4G1cNAc-R) sugar chain epitope. However, the removal of terminal sialic acid residues from mouse laminin-1 resulted in a complete loss of antibody binding by most patients' sera. To identify real autoantigens of these antibodies, lysates from ectopic and eutopic endometrium, and ovarian cyst, peritoneal fluids, and sera from infertile patients with endometriosis or healthy controls were examined by Western blot analysis. Autoantigens were not detected, therefore, we analyze the structure of the oligosaccharide chain epitope using HPLC/MS. Based on the determined epitope structure, we will predict the real autoantigens.2. We studied the effect of a recently established anti-laminin-1 mouse monoclonal IgM (AK8), an affinity-purified anti-laminin-1 IgG from the … More serum of an infertile patient with endometriosis, and a polyclonal anti-laminin rabbit IgG on mouse embryo implantation in vitro. AK8 and the polyclonal anti-laminin rabbit IgG did not have an effect on blastocyst hatching, but strongly inhibited the blastocyst adhesion and outgrowth in about 100 % of the blastocysts. On the other hand, the affinity-purified IgG specific for the oligosaccharide chains of laminin-1 did not affect blastocyst hatching or adhesion, but inhibited the area of outgrowth in about 30 % of the blastocysts.3. Sera from some infertile patients with endometriosis cross-reacted with the peptide moiety of laminin γl chain. Laminin-1 contains about 20 angiogenic peptide sequences. Among of them, angiogenic peptide sequence of γ1 chain (C16 peptide) binds to integrin α5β1 and αvβ3 of endothelial cells and most potently promotes angiogenesis. Angiogenesis is critical for the initiation and progression of endometriosis. We established an anti-C16 peptide monoclonal IgM (anti-C16 mAb) by immunizing mice with BSA-conjugated C16 peptide. Anti-C16 mAb inhibited in vitro tube formation of human umbilical endothelial cells (HUVECs) and in vivo angiogenesis in nude mice. We will investigate the inhibitory effect of anti-C16 mAb on angiogenesis in human endometrial fragments or endometriotic lesions in vitro. Less

1.子宫内膜异位症不孕患者的抗层粘连蛋白-1自身抗体识别小鼠层粘连蛋白-1的N-连接寡糖链。一定百分比的患者表达识别α-Gal（Galal-3Ga 1 β1- 4GlcNAc-R）糖链表位的天然抗体。然而，从小鼠层粘连蛋白-1去除末端唾液酸残基导致大多数患者血清完全丧失抗体结合。为了鉴定这些抗体的真实的自身抗原，通过Western印迹分析检测异位和在位子宫内膜、卵巢囊肿、腹腔液和患有子宫内膜异位症的不孕患者或健康对照的血清的裂解物。未检测到自身抗原，因此，我们利用HPLC/MS分析寡糖链表位的结构，根据确定的表位结构，预测真实的自身抗原.我们研究了最近建立的抗层粘连蛋白-1小鼠单克隆IgM（AK 8）的作用，这是一种来自大肠杆菌的亲和纯化的抗层粘连蛋白-1 IgG ...更多信息子宫内膜异位症不孕患者血清和多克隆抗层粘连蛋白兔IgG对小鼠胚胎体外着床的影响。AK 8和多克隆抗层粘连蛋白兔IgG对囊胚孵化没有影响，但在约100%的囊胚中强烈抑制囊胚粘附和生长。另一方面，亲和纯化的层粘连蛋白-1寡糖链特异性IgG不影响囊胚孵化或粘附，但抑制了约30%的囊胚生长面积.部分子宫内膜异位症不孕患者血清与层粘连蛋白γ 1链肽段有交叉反应。层粘连蛋白-1含有约20个血管生成肽序列。其中，血管生成肽γ1链（C16肽）与内皮细胞的整合素α5β1和αvβ3结合，促进血管生成的作用最强。血管生成对于子宫内膜异位症的发生和发展至关重要。我们用BSA标记的C16肽免疫小鼠，建立了抗C16肽的单克隆IgM（anti-C16 mAb）。抗C16单克隆抗体在体外抑制人脐静脉内皮细胞（HUVECs）的管形成和在裸鼠体内的血管生成。我们将在体外研究抗C16单克隆抗体对人子宫内膜碎片或增生性病变血管生成的抑制作用。少

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of a murine anti-laminin-1 monoclonal antibody (AK8) produced by immunization with mouse-derived laminin-1.

DOI：
10.1080/17402520400014168
发表时间：
2005-03
期刊：
Clinical & developmental immunology
影响因子：
0
作者：
Kondo A;Inagaki J;Kobayashi K;Tsukamoto H;Yamamoto D;Nakatsuka M;Suzuki N;Nomizu M;Amano S;Matsubayashi H;Yasuda T;Lopez LR;Shoenfeld Y;Makino T;Matsuura E
通讯作者：
Matsuura E

Antigenic structure recognized by anti-β2-glycoprotein I auto-antibodies.

抗 β2-糖蛋白 I 自身抗体识别的抗原结构。