Mercury Exposure and Antinuclear Antibodies among Females of Reproductive Age in the United States: NHANES

Abstract

Background: Immune dysregulation associated with mercury has been suggested, although data in the general population are lacking. Chronic exposure to low levels of methylmercury (organic) and inorganic mercury is common, such as through fish consumption and dental amalgams.

Objective: We examined associations between mercury biomarkers and antinuclear antibody (ANA) positivity and titer strength.

Methods: Among females 16-49 years of age (n = 1,352) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, we examined cross-sectional associations between mercury and ANAs (indirect immunofluorescence; cutoff ≥ 1:80). Three biomarkers of mercury exposure were used: hair (available 1999-2000) and total blood (1999-2004) predominantly represented methylmercury, and urine (1999-2002) represented inorganic mercury. Survey statistics were used. Multivariable modeling adjusted for several covariates, including age and omega-3 fatty acids.

Results: Sixteen percent of females were ANA positive; 96% of ANA positives had a nuclear speckled staining pattern. Geometric mean (geometric SD) mercury concentrations were 0.22 (0.03) ppm in hair, 0.92 (0.05) μg/L blood, and 0.62 (0.04) μg/L urine. Hair and blood, but not urinary, mercury were associated with ANA positivity (sample sizes 452, 1,352, and 804, respectively), after adjusting for confounders: for hair, odds ratio (OR) = 4.10 (95% CI: 1.66, 10.13); for blood, OR = 2.32 (95% CI: 1.07, 5.03) comparing highest versus lowest quantiles. Magnitudes of association were strongest for high-titer (≥ 1:1,280) ANA: hair, OR = 11.41 (95% CI: 1.60, 81.23); blood, OR = 5.93 (95% CI: 1.57, 22.47).

Conclusions: Methylmercury, at low levels generally considered safe, was associated with subclinical autoimmunity among reproductive-age females. Autoantibodies may predate clinical disease by years; thus, methylmercury exposure may be relevant to future autoimmune disease risk.

Figure 1

Associations of antinuclear antibody (ANA) positivity with log-transformed hair and total blood mercury (Hg), adjusted for Model B covariates. (A) Hair Hg (1999–2000; n = 452). (B) Total blood Hg (1999–2004; n = 1,352). Solid black lines represent the smoothing trends estimated from the natural spline with 3 degrees of freedom (df) for hair Hg and 4 df for total blood Hg (knots at 25th, 50th, and 75th percentiles); red dotted lines represent 95% CIs; and bars represent the weighted density distribution for Hg. The dose–response relationship for both hair and total blood Hg increased in a statistically significant fashion within the lower ranges of Hg exposure.

Figure 2

Weighted proportions of antinuclear antibody (ANA) positivity and titer categories according to mercury (Hg) exposure quantiles. (A) Hair Hg (1999–2000; n = 452). (B) Total blood Hg (1999–2004; n = 1,352). (C) Urinary Hg (1999–2002; n = 804).