Dataset Information

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: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).

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.

Similar Datasets

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