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Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in Faroese children.

ABSTRACT: Methylmercury, polychlorinated biphenyls (PCBs), and perfluorinated compounds (PFCs) are ubiquitous and persistent environmental chemicals with known or suspected toxic effects on the nervous system and the immune system. Animal studies have shown that tissue damage can elicit production of autoantibodies. However, it is not known if autoantibodies similarly will be generated and detectable in humans following toxicant exposures. Therefore, we conducted a pilot study to investigate if autoantibodies specific for neural and non-neural antigens could be detected in children at age 7 years who have been exposed to environmental chemicals. Both prenatal and age-7 exposures to mercury, PCBs, and PFCs were measured in 38 children in the Faroe Islands who were exposed to widely different levels of these chemicals due to their seafood-based diet. Concentrations of IgM and IgG autoantibodies specific to both neural (neurofilaments, cholineacetyltransferase, astrocyte glial fibrillary acidic protein, and myelin basic protein) and non-neural (actin, desmin, and keratin) antigens were measured and the associations of these autoantibody concentrations with chemical exposures were assessed using linear regression. Age-7 blood-mercury concentrations were positively associated with titers of multiple neural- and non-neural-specific antibodies, mostly of the IgM isotype. Additionally, prenatal blood-mercury and -PCBs were negatively associated with anti-keratin IgG and prenatal PFOS was negatively associated with anti-actin IgG. These exploratory findings demonstrate that autoantibodies can be detected in the peripheral blood following exposure to environmental chemicals. The unexpected association of exposures with antibodies specific for non-neural antigens suggests that these chemicals may have toxicities that have not yet been recognized.

SUBMITTER: Osuna CE

PROVIDER: S-EPMC4334810 | biostudies-other | 2014 Nov

REPOSITORIES: biostudies-other

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Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in Faroese children.

Osuna Christa E CE Grandjean Philippe P Weihe Pál P El-Fawal Hassan A N HA

Toxicological sciences : an official journal of the Society of Toxicology 20140814 1

Methylmercury, polychlorinated biphenyls (PCBs), and perfluorinated compounds (PFCs) are ubiquitous and persistent environmental chemicals with known or suspected toxic effects on the nervous system and the immune system. Animal studies have shown that tissue damage can elicit production of autoantibodies. However, it is not known if autoantibodies similarly will be generated and detectable in humans following toxicant exposures. Therefore, we conducted a pilot study to investigate if autoantibo ...[more]

PMID: 25124724

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Project description:BackgroundAlthough prenatal methylmercury exposure has been linked to poorer intellectual function in several studies, data from two major prospective, longitudinal studies yielded contradictory results. Associations with cognitive deficits were reported in a Faroe Islands cohort, but few were found in a study in the Seychelles Islands. It has been suggested that co-exposure to another contaminant, polychlorinated biphenyls (PCBs), may be responsible for the positive findings in the former study and that co-exposure to nutrients in methylmercury-contaminated fish may have obscured and/or protected against adverse effects in the latter.ObjectivesWe aimed to determine the degree to which co-exposure to PCBs may account for the adverse effects of methylmercury and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure these effects in a sample of Inuit children in Arctic Québec.MethodsIQ was estimated in 282 school-age children from whom umbilical cord blood samples had been obtained and analyzed for mercury and other environmental exposures.ResultsPrenatal mercury exposure was related to poorer estimated IQ after adjustment for potential confounding variables. The entry of DHA into the model significantly strengthened the association with mercury, supporting the hypothesis that beneficial effects from DHA intake can obscure adverse effects of mercury exposure. Children with cord mercury ≥ 7.5 μg/L were four times as likely to have an IQ score < 80, the clinical cut-off for borderline intellectual disability. Co-exposure to PCBs did not alter the association of mercury with IQ.ConclusionsTo our knowledge, this is the first study to document an association of prenatal mercury exposure with poorer performance on a school-age assessment of IQ, a measure whose relevance for occupational success in adulthood is well established. This association was seen at levels in the range within which many U.S. children of Asian-American background are exposed.

Project description:IntroductionPrenatal exposure to environmental chemicals may be associated with allergies later in life. We aimed to examine the association between prenatal dietary exposure to mixtures of chemicals and allergic or respiratory diseases up to age 5.5 y.MethodsWe included 11,638 mother-child pairs from the French "Étude Longitudinale Française depuis l'Enfance" (ELFE) cohort. Maternal dietary exposure during pregnancy to eight mixtures of chemicals was previously assessed. Allergic and respiratory diseases (eczema, food allergy, wheezing and asthma) were reported by parents between birth and age 5.5 years. Associations were evaluated with adjusted logistic regressions. Results are expressed as odds ratio (OR[95%CI]) for a variation of one SD increase in mixture pattern.ResultsMaternal dietary exposure to a mixture composed mainly of trace elements, furans and polycyclic aromatic hydrocarbons (PAHs) was positively associated with the risk of eczema (1.10 [1.05; 1.15]), this association was consistent across sensitivity analyses. Dietary exposure to one mixture of pesticides was positively associated with the risk of food allergy (1.10 [1.02; 1.18]), whereas the exposure to another mixture of pesticides was positively but slightly related to the risk of wheezing (1.05 [1.01; 1.08]). This last association was not found in all sensitivity analyses. Dietary exposure to a mixture composed by perfluoroalkyl acids, PAHs and trace elements was negatively associated with the risk of asthma (0.89 [0.80; 0.99]), this association was consistent across sensitivity analyses, except the complete-case analysis.ConclusionWhereas few individual chemicals were related to the risk of allergic and respiratory diseases, some consistent associations were found between prenatal dietary exposure to some mixtures of chemicals and the risk of allergic or respiratory diseases. The positive association between trace elements, furans and PAHs and the risk of eczema, and that between pesticides mixtures and food allergy need to be confirmed in other studies. Conversely, the negative association between perfluoroalkyl acids, PAHs and trace elements and the risk of asthma need to be further explored.

Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders. The buffy coat and plasma samples were separated and stored at −80°C. DNA (100 ng-500 ng) was extracted from cord white blood cells. Microarrays have been performed to investigate fourteen samples, which were classified as two groups according to cotinine exposure dosage (7 versus 7 : high exposure verses low exposure).

Project description:BACKGROUND:Prenatal exposure to environmental contaminants can have deleterious effects on child development. While psychomotor, cognitive and behavioural outcomes have been investigated in relation to chronic exposure, the associations with visual functions remains unclear. The present study's aim was to assess the associations of prenatal exposure to legacy persistent organic pollutants and heavy metals with visual acuity in Canadian infants. The potential protective effects of selenium against mercury toxicity were also examined. METHODS:Participants (mean corrected age?=?6.6?months) were part of the Maternal-Infant Research on Environmental Chemicals (MIREC) study. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), lead and mercury were measured in maternal blood during pregnancy, as well as in the cord blood. The Teller acuity card test (TAC) (n?=?429) and the visual evoked potentials in a sub-group (n?=?63) were used to estimate behavioural and electrophysiological visual acuity, respectively. Multivariable linear regression models were used to investigate the relationship between exposure to each contaminant and visual acuity measures, while controlling for potential confounders. Breastmilk selenium, which was available for about half of the TAC and VEP samples, was also taken into account in the mercury models as exploratory analyses. RESULTS:We observed no significant associations between exposure to any contaminants and TAC. Analyses revealed a negative trend (p values <?0.1) between cord blood lead and mercury and electrophysiological visual acuity, whereas PCB and PBDE showed no association. When adding breastmilk selenium concentration to the mercury models, this association became statistically significant for cord concentrations (??=?-?3.41, 95% CI?=?-?5.96,-0.86), but also for blood levels at 1st and 3rd trimesters of pregnancy (??=?-?3.29, 95% CI?=?-?5.69,-0.88). However, further regression models suggested that this change in estimates might not be due to adjustment for selenium, but instead to a change in the study sample. CONCLUSIONS:Our results suggest that subtle, but detectable alterations of infant electrophysiological visual acuity can be identified in a population prenatally exposed to low mercury concentrations. Compared to behavioural visual acuity testing, electrophysiological assessment may more sensitive in detecting visual neurotoxicity in relation with prenatal exposure to mercury.

Dataset Information

Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in Faroese children.

Publications

Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in Faroese children.

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