Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect.
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.
Rothenberg
Sheldon P
SP
Department of Medicine, State University of New York Downstate Medical Center, Brooklyn 11203, USA. srothenberg@downstate.edu
da Costa
Maria P
MP
Sequeira
Jeffrey M
JM
Cracco
Joan
J
Roberts
Jaclyn L
JL
Weedon
Jeremy
J
Quadros
Edward V
EV
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
D001323:Autoantibodies; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid