Toxic effects on immune system development may seriously impair human health, but immunotoxicity is rarely considered in risk assessment of environmental chemicals. A main problem is the absence of systematic epidemiological evidence. We have successfully established birth cohorts for prospective studies in a unique fishing population exposed to marine contaminants - the Faroe Islands - and we have demonstrated that vaccine responses in children can be applied as a model of immunotoxicity associated with polychlorinated biphenyl (PCB) exposure. This competitive renewal application extends the follow-up of the same birth cohort of >600 children for sustained serum concentrations of antibodies against vaccines and in regard to allergic disease up to adolescence. In a second birth cohort of 500 children recently established, we will test whether the immunotoxicant exposure at age 18 months represents a main window of vulnerability in regard to the subsequent serum antibody concentrations. Further, we will explore the impact of past and cumulated exposure levels on responses to a vaccine booster, as reflected by specific antibody concentrations and by changes in lymphocyte populations and cytokine production. Likewise, clinical evidence of allergy development, including serum concentrations of total and specific IgEs against common antigens, will be evaluated in regard to exposures during prenatal and postnatal time windows. In addition to already confirmed immunotoxicants PCBs and methylmercury, the study will examine the possible immunotoxicity of the total AhR (dioxin-related) activity in serum and of perfluorinated compounds and butyltins. Vaccine antibody assays for tetanus and diphtheria toxoids will be expanded to include Pneumococcus polysaccharide antigens. Because this study relies on two existing birth cohorts with banked blood samples and background information already collected - in part financed by other sources - the proposed research will cover a time span of 14 years to allow consideration of exposures incurred prenatally and outcomes followed until adolescence. The cumulated evidence will therefore likely be of substantial importance for the understanding of developmental immunotoxicity in humans and for risk assessment of immunotoxic agents.

Public Health Relevance

Due to the lack of systematic data, immunotoxicity is rarely taken into account in risk assessment. This systematic study aims at providing a stronger basis for prevention of immune system dysfunctions related to environmental chemicals. It will examine antibody concentrations and cellular responses to routine childhood immunizations as well as the occurrence of allergic disease up to adolescence in regard to exposures to environmental chemicals prenatally and at different ages after birth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES012199-08
Application #
8449687
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Gray, Kimberly A
Project Start
2003-04-01
Project End
2016-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
8
Fiscal Year
2013
Total Cost
$419,518
Indirect Cost
$19,492
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Grandjean, Philippe (2016) Paracelsus Revisited: The Dose Concept in a Complex World. Basic Clin Pharmacol Toxicol 119:126-32
Oulhote, Y; Shamim, Z; Kielsen, K et al. (2016) Children's white blood cell counts in relation to developmental exposures to methylmercury and persistent organic pollutants. Reprod Toxicol :
Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Petersen, Maria Skaalum et al. (2016) Shorter duration of breastfeeding at elevated exposures to perfluoroalkyl substances. Reprod Toxicol :
Kielsen, Katrine; Shamim, Zaiba; Ryder, Lars P et al. (2016) Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates. J Immunotoxicol 13:270-3
Karlsen, Martina; Grandjean, Philippe; Weihe, Pal et al. (2016) Early-life exposures to persistent organic pollutants in relation to overweight in preschool children. Reprod Toxicol :
Dalgård, Christine; Petersen, Maria Skaalum; Steuerwald, Ulrike et al. (2016) Umbilical Cord Serum 25-Hydroxyvitamin D Concentrations and Relation to Birthweight, Head Circumference and Infant Length at Age 14 Days. Paediatr Perinat Epidemiol 30:238-45
Grandjean, Philippe; Clapp, Richard (2015) Perfluorinated Alkyl Substances: Emerging Insights Into Health Risks. New Solut 25:147-63
Mogensen, Ulla B; Grandjean, Philippe; Nielsen, Flemming et al. (2015) Breastfeeding as an Exposure Pathway for Perfluorinated Alkylates. Environ Sci Technol 49:10466-73
Mogensen, Ulla B; Grandjean, Philippe; Heilmann, Carsten et al. (2015) Structural equation modeling of immunotoxicity associated with exposure to perfluorinated alkylates. Environ Health 14:47
Tang-Péronard, Jeanett L; Heitmann, Berit L; Jensen, Tina K et al. (2015) Prenatal exposure to persistent organochlorine pollutants is associated with high insulin levels in 5-year-old girls. Environ Res 142:407-13

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