2005年
Pregnancy loss and endometriosis - Pathogenic role of anti-laminin-1 autoantibodies
AUTOIMMUNE DISEASES AND TREATMENT: ORGAN-SPECIFIC AND SYSTEMIC DISORDERS
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- 巻
- 1051
- 号
- 開始ページ
- 174
- 終了ページ
- 184
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1196/annals.1361.059
- 出版者・発行元
- NEW YORK ACAD SCIENCES
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.
- リンク情報
- ID情報
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- DOI : 10.1196/annals.1361.059
- ISSN : 0077-8923
- Web of Science ID : WOS:000233393100019