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. 2008 Oct;79(1):85-92.
doi: 10.1016/j.jri.2008.08.002. Epub 2008 Sep 18.

Autoantibodies to folate receptor during pregnancy and neural tube defect risk

Robert M Cabrera  1 , Gary M Shaw, Johnathan L Ballard, Suzan L Carmichael, Wei Yang, Edward J Lammer, Richard H Finnell
Affiliations

Autoantibodies to folate receptor during pregnancy and neural tube defect risk

Robert M Cabrera et al. J Reprod Immunol. 2008 Oct.

Abstract

Periconceptional folic acid can reduce the occurrence of neural tube defects (NTDs) by up to 70%, and autoantibodies for folate receptors (FRs) have been observed in serum from women with a pregnancy complicated by an NTD. This population-based cohort study has examined serum from pregnant mothers for autoantibodies to FRs, antibodies to bovine folate binding protein (FBP), and inhibition of folic acid binding to FR and FBP in association with NTD risk. The mid-gestational maternal serum specimens used for this study were collected during the 15-18th week of pregnancy. Samples were obtained from the California Birth Defects Monitoring Program; 29 mothers had a pregnancy complicated by spina bifida and 76 mothers had unaffected children. The presence of IgG and IgM antibodies to human FR, bovine FBP, and inhibition of folic acid binding to FR and FBP was determined. Higher activity of IgM to FBP in cases verses controls was observed (P=0.04). Higher activity of IgM and IgG autoantibodies to FR was observed (P<0.001 and P=0.04, respectively). Risk estimates at two standard deviations above average control antibody concentrations were OR=2.07 (CI=1.02, 4.06) for anti-FBP IgM, OR=2.15 (CI=1.02, 4.69) for anti-FR IgG and OR=3.19 (CI=1.47, 6.92) for anti-FR IgM. These data support the hypothesis that high titers of antibodies and blocking of folic acid binding to FRs by maternal serum should be regarded as risk factors for NTDs.

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Figures

Figure 1
Figure 1. Antibody detection and folic acid binding inhibition
Images show the functional testing results of the assay. The vertical axes of the graphs represent detected signal intensities (8-bit). (A) A serial dilution (1:10 to 1:640) of a positive serum sample is shown for IgG antibodies against bovine folate binding protein (FBP). Fluorescent intensities were extracted and plotted against a regression line with standard errors to generate the graph. (B) Results are displayed for folic acid binding to FBP. A dilution series of folic acid was used to quantify interactions. Fluorescent intensities were extracted, log-transformed and fitted against a sigmoid regression curve for the graph (GraphPad Software, San Diego, CA).
See this image and copyright information in PMC

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