title: Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect.
abstract: BACKGROUND
  In the absence of clinical folate deficiency, periconceptional supplementation with folic acid reduces a woman's risk of having an infant with a neural-tube defect. Since antiserum to folate receptors induces embryo resorption and malformations in rats, we hypothesized that autoantibodies against folate receptors in women may be associated with pregnancy complicated by a neural-tube defect.
  
  
  METHODS
  Serum from 12 women who were or had been pregnant with a fetus with a neural-tube defect and from 24 control women (20 with current or prior normal pregnancies and 4 who were nulligravid) was analyzed for autoantibodies by incubation with human placental folate receptors radiolabeled with [3H]folic acid. The properties of these autoantibodies were characterized by incubating serum and the autoantibodies isolated from serum with placental membranes, ED27 cells, and KB cells, which express the folate receptors.
  
  
  RESULTS
  Serum from 9 of 12 women with a current or previous affected pregnancy (index subjects) and 2 of 20 control subjects contained autoantibodies against folate receptors (P<0.001). The autoantibodies blocked the binding of [3H]folic acid to folate receptors on placental membranes and on ED27 and KB cells incubated at 4 degrees C and blocked the uptake of [3H]folic acid by KB cells when incubated at 37 degrees C.
  
  
  CONCLUSIONS
  Serum from women with a pregnancy complicated by a neural-tube defect contains autoantibodies that bind to folate receptors and can block the cellular uptake of folate. Further study is warranted to assess whether the observed association between maternal autoantibodies against folate receptors and neural-tube defects reflects a causal relation.
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, Brooklyn 11203, USA. srothenberg@downstate.edu
authors.forename: Sheldon P
authors.initials: SP
authors.lastname: Rothenberg
authors.forename: Maria P
authors.initials: MP
authors.lastname: da Costa
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Sequeira
authors.forename: Joan
authors.initials: J
authors.lastname: Cracco
authors.forename: Jaclyn L
authors.initials: JL
authors.lastname: Roberts
authors.forename: Jeremy
authors.initials: J
authors.lastname: Weedon
authors.forename: Edward V
authors.initials: EV
authors.lastname: Quadros
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007624:KB Cells; D009436:Neural Tube Defects / Q000276:immunology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000097:blood / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology
chemical_list: D001323:Autoantibodies; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid