Anti-laminin-1 autoantibodies, pregnancy loss and endometriosis.
Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, alpha1, beta1 and gamma11 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-alpha1, -beta1 and -gamma1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-alpha1, -beta1 and -gamma1 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 alpha1 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.
Inagaki
Junko
J
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Kondo
Akane
A
Lopez
Luis R
LR
Shoenfeld
Yehuda
Y
Matsuura
Eiji
E
D000026:Abortion, Habitual / Q000276:immunology*; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D004715:Endometriosis / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007247:Infertility, Female / Q000209:etiology / Q000276:immunology; D007797:Laminin / Q000737:chemistry / Q000276:immunology*; D008958:Models, Molecular; D011247:Pregnancy; D021122:Protein Subunits
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007797:Laminin; D021122:Protein Subunits; C121346:laminin 1