Assessment of a Biomarker of Prenatal Mercury Immunotoxicity: a Cross-Sectional Study

Background: Evaluating the potential impacts of prenatal exposures on the maternal and fetal immune systems (both as a unit and separately) has been hampered by lack of information on the relative contribution of each component to serum biomarkers such as IgG and IgM antibodies. We have examined the effects of prenatal mercury exposures on immune biomarkers in serum prepared from cord blood and maternal blood samples in a population exposed to methylmercury. Mercury is a ubiquitous environmental contaminant with known neurodevelopmental effects at high exposures and its role in the development of autism/autism spectrum disorders remains controversial. Recent studies on the toxic properties of mercury have highlighted the implications at lower exposures particularly on the immune system. Low level prenatal exposure through maternal contaminated fish consumption has the potential to impact the immune system of the fetus, potentially increasing susceptibility to disease. Many studies have been undertaken to identify a reliable biomarker of the immunotoxic effects of mercury. We have previously reported that antigen-specific autoantibodies (anti-nuclear, ANA) may be informative biomarkers of mercury-induced immunotoxicity.

Objectives: In this study, we assessed the effects of prenatal exposure to mercury on total and ANA immunoglobulins in a cross-sectional sample from a prospective mother-infant cohort study in Amazonian Brazil.

Methods: We compared maternal and cord blood mercury and antibody levels with maternal covariates obtained by questionnaire. Serum levels of total immunoglobulin were measured by ELISA and ANA levels by indirect immunofluorescence of serial 2-fold dilutions on HEp-2 slides according to standard clinical methods.

Results: Blood mercury concentrations were higher in cord blood than in maternal blood (geometric mean of mercury in mothers was 6.9 and in cord blood it was 9.6 ug/L). We found that total and ANA IgG, but not IgM, levels were correlated with both maternal and cord blood immunoglobulin. Moreover, total IgG level in cord blood was significantly associated with fetal mercury level. ANA titer in either maternal or cord blood was not significantly associated with either maternal or cord blood mercury levels.

Conclusions: These findings are consistent with research on the ability of IgG, but not IgM, to cross the placenta in the absence of infection and thus indicate that measurements of both immunoglobulins may provide insight on differential responses of fetuses and mothers to a toxicant that crosses the placental barrier. These data provide further evidence for the immunotoxicity of mercury at low dose, and the first evidence for such effects during prenatal development. This research was supported by grants from the National Institutes of Environmental Health Sciences K99 ES015426 (JFN) and the Johns Hopkins University Center for a Livable Future (JFN).