IgG Anti‐laminin‐1 Autoantibody and Recurrent Miscarriages

Inagaki, Jiro; Matsuura, Eiji; Nomizu, Motoyoshi; Sugiura‐Ogasawara, Mayumi; Katano, Kinue; Kaihara, Keiko; Kobayashi, Kazuo; Yasuda, Tatsuji; Aoki, Koji

doi:10.1111/j.8755-8920.2001.450406.x

Cited by 40 publications

(33 citation statements)

References 23 publications

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“…Anti-laminin-1 Abs from the immunized mice caused a higher fetal resorption rate with lower embryonic and placental weights (Matalon et al 2003). We have also demonstrated that elevated serum levels of IgG anti-laminin-1 Abs are significantly associated with recurrent firsttrimester miscarriages and infertility with endometriosis (Inagaki et al 2001. These observations suggest that anti-laminin-1 autoAbs may be responsible for reproductive failure, interfering with the early stages of pregnancy.…”

Section: Introductionmentioning

confidence: 60%

“…ELISA for anti-laminin-1 antibodies was performed as described by Inagaki et al (2001). Briefly, polystyrene plates (Immulon 1B, Thermo Electron, San Jose, CA) were coated with the purified laminin-1 (10 mg/ml, 50 ml/well) by overnight incubation at 48C.…”

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

“…ELISA was first performed on microtiter plates coated with various isoforms of laminin-1 to characterize the specificity of AK8 mAb, as previously described (Inagaki et al 2001). AK8 mAb only bound to mouse laminin-1 (a1, b1, g1), but not to other human laminin isoforms, i.e.…”

Section: Specificity Of Ak8 Mabmentioning

confidence: 99%

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Characterization of a Murine Anti‐laminin‐1 Monoclonal Antibody (AK8) Produced by Immunization with Mouse‐derived Laminin‐1

Kondo

Inagaki

Kobayashi

et al. 2005

Journal of Immunology Research

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Laminin-1 is a structural glycoprotein that forms an integral part of the scaffolding of basement membranes, and plays an important role during embryonic development. We have recently demonstrated a significant association between anti-laminin-1 antibodies (Abs) and reproductive failure, such as recurrent spontaneous abortions and infertility-associated endometriosis in both human and mouse studies. In the present study, we established an IgM (m, k) monoclonal anti-laminin-1 Ab (AK8) by immunizing mice with mouse Engelbreth -Holm -Swarm sarcoma (EHS)-derived laminin-1. The AK8 monoclonal antibody (mAb) reacted with particular peptide sequences from the globular G domain of mouse laminin-a1 chain of using ELISA and Western blot techniques. The peptide tertiary structure of the epitope recognized by AK8 mAb was predicted using eight synthesized domain peptide sequences and three consensus sequences obtained by phage displayed random peptide library. Basement membranes of endometrium of pregnant mice and humans were immunostained with AK8 mAb. Thus, AK8 mAb recognized a common structure present in the G domain of the laminin-a1 chain in both mice and humans. The passive immunization of mice with AK8 mAb may represent a suitable animal model for anti-laminin-1 Ab-mediated reproductive failure.

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Section: Introductionmentioning

confidence: 60%

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

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Characterization of a Murine Anti‐laminin‐1 Monoclonal Antibody (AK8) Produced by Immunization with Mouse‐derived Laminin‐1

Kondo

Inagaki

Kobayashi

et al. 2005

Journal of Immunology Research

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“…Our recent clinical study showed that IgG anti-laminin-1 antibodies in blood are significantly associated with the recurrent first-trimester miscarriages in humans (Inagaki et al, 2001). All of these observations suggest that IgG antilaminin-1 antibodies may be responsible for reproductive failure, interfering with an early stage of pregnancy.…”

Section: Clinical Significance Of Igg Anti-laminin-1 Antibodies Recurmentioning

confidence: 99%

“…Solid lines show the mean value. (Inagaki et al, 2001). with the function of laminin-1 to disrupt early reproductive stages and be involved in the development of endometriosis.…”

Section: Infertility Caused By Endometriosismentioning

confidence: 99%

Anti-laminin-1 autoantibodies, pregnancy loss and endometriosis

Inagaki¹,

Kondo²,

Lopez³

et al. 2004

Autoimmunity Reviews

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Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, a1, b1 and g1 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-a1, -b1 and -g1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-a1, -b1 and -g1 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 a1 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 autoimmunemediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.

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