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


CONCLUSIONS
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.


CONCLUSIONS
These data indicate that direct immune effects in untreated CD women may compromise placental function.
Anjum
Naheed
N
Maternal and Fetal Health Research Group, University of Manchester, Research Floor, St Mary's Hospital, Manchester M130JH, UK. naheed_azhar_9@hotmail.com
Baker
Philip N
PN
Robinson
Nicola J
NJ
Aplin
John D
JD
D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000502:physiology; D002446:Celiac Disease / Q000201:enzymology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D008871:Microvilli / Q000276:immunology; D010920:Placenta / Q000201:enzymology / Q000276:immunology*; D011247:Pregnancy; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000276:immunology*; D014327:Trophoblasts / Q000201:enzymology / Q000276:immunology*
D001323:Autoantibodies; D007070:Immunoglobulin A; D011503:Transglutaminases