Maternal celiac disease autoantibodies bind directly to syncytiotrophoblast and inhibit placental tissue transglutaminase activity

Naheed Anjum, Philip N. Baker, Nicola J. Robinson, John D. Aplin

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background: Celiac disease (CD) occurs in as many as 1 in 80 pregnant women and is associated with poor pregnancy outcome, but it is not known if this is an effect on maternal nutrient absorption or, alternatively, if the placenta is an autoimmune target. The major autoantigen, tissue transglutaminase (tTG), has previously been shown to be present in the maternal-facing syncytiotrophoblast plasma membrane of the placenta. Methods: ELISA was used to demonstrate the presence of antibodies to tissue transglutaminase in a panel of CD sera. Immunohistochemistry was used to evaluate the binding of IgA autoantibodies from CD serum to term placenta. In addition, novel direct binding and activity assays were developed to mimic the in vivo exposure of the villous placenta to maternal autoantibody. Results and Discussion: CD IgA autoantibodies located to the syncytial surface of the placenta significantly more than IgA antibodies in control sera (P <0.0001). The distribution of antigen was similar to that observed using a monoclonal antibody to tissue transglutaminase. Staining was reduced by pre-absorption of CD serum with recombinant human tissue transglutaminase. In direct binding assays, autoimmune immunoglobulin A (IgA) from the maternal compartment became associated with antigen at the syncytial surface of the placenta, as a result of which transglutaminase activity at this site was inhibited. Conclusion: These data indicate that direct immune effects in untreated CD women may compromise placental function. © 2009 Anjum et al; licensee BioMed Central Ltd.
    Original languageEnglish
    Article number16
    JournalReproductive Biology and Endocrinology
    Volume7
    DOIs
    Publication statusPublished - 19 Feb 2009

    Keywords

    • blood: Autoantibodies
    • enzymology: Celiac Disease
    • Enzyme-Linked Immunosorbent Assay
    • Female
    • Humans
    • immunology: Immunoglobulin A
    • immunology: Microvilli
    • enzymology: Placenta
    • Pregnancy
    • antagonists & inhibitors: Transglutaminases
    • enzymology: Trophoblasts

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