Autoantibodies against Folate Receptors in Women with a Pregnancy Complicated by a Neural-Tube Defect
Sheldon P. Rothenberg, M.D., Maria P. da Costa, M.D., Jeffrey M. Sequeira, M.S., Joan Cracco, M.D., Jaclyn L. Roberts, M.D., Jeremy Weedon, Ph.D., and Edward V. Quadros, Ph.D.
Background In the absence of clinical folate deficiency, periconceptionalsupplementation with folic acid reduces a woman's risk of havingan infant with a neural-tube defect. Since antiserum to folatereceptors induces embryo resorption and malformations in rats,we hypothesized that autoantibodies against folate receptorsin women may be associated with pregnancy complicated by a neural-tubedefect.
Methods Serum from 12 women who were or had been pregnant witha fetus with a neural-tube defect and from 24 control women(20 with current or prior normal pregnancies and 4 who werenulligravid) was analyzed for autoantibodies by incubation withhuman placental folate receptors radiolabeled with [3H]folicacid. The properties of these autoantibodies were characterizedby incubating serum and the autoantibodies isolated from serumwith placental membranes, ED27 cells, and KB cells, which expressthe folate receptors.
Results Serum from 9 of 12 women with a current or previousaffected pregnancy (index subjects) and 2 of 20 control subjectscontained autoantibodies against folate receptors (P<0.001).The autoantibodies blocked the binding of [3H]folic acid tofolate receptors on placental membranes and on ED27 and KB cellsincubated at 4°C and blocked the uptake of [3H]folic acidby KB cells when incubated at 37°C.
Conclusions Serum from women with a pregnancy complicated bya neural-tube defect contains autoantibodies that bind to folatereceptors and can block the cellular uptake of folate. Furtherstudy is warranted to assess whether the observed associationbetween maternal autoantibodies against folate receptors andneural-tube defects reflects a causal relation.
Source Information
From the Departments of Medicine (S.P.R., M.P.C., J.M.S., E.V.Q.) and Obstetrics and Gynecology (J.L.R.), the Division of Pediatric Neurology (J.C.), and the Scientific Computing Center (J.W.), State University of New York Downstate Medical Center, Brooklyn.
Address reprint requests to Dr. Rothenberg at SUNY Downstate Medical Center, 450 Clarkson Ave., Box 20, Brooklyn, NY 11203, or at srothenberg{at}downstate.edu.
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