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
Osuna, Christa E; Grandjean, Philippe; Weihe, Pál et al. (2014) Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in Faroese children. Toxicol Sci 142:158-66
Grandjean, Philippe; Clapp, Richard (2014) Changing interpretation of human health risks from perfluorinated compounds. Public Health Rep 129:482-5
Kvist, L; Giwercman, A; Weihe, P et al. (2014) Exposure to persistent organic pollutants and sperm sex chromosome ratio in men from the Faroe Islands. Environ Int 73:359-64
Tang-Peronard, Jeanett L; Heitmann, Berit L; Andersen, Helle R et al. (2014) Association between prenatal polychlorinated biphenyl exposure and obesity development at ages 5 and 7 y: a prospective cohort study of 656 children from the Faroe Islands. Am J Clin Nutr 99:5-13
Kim, Byung-Mi; Choi, Anna L; Ha, Eun-Hee et al. (2014) Effect of hemoglobin adjustment on the precision of mercury concentrations in maternal and cord blood. Environ Res 132:407-12
Bellanger, Martine; Pichery, Celine; Aerts, Dominique et al. (2013) Economic benefits of methylmercury exposure control in Europe: monetary value of neurotoxicity prevention. Environ Health 12:3
Grandjean, Philippe; Andersen, Elisabeth Wreford; Budtz-Jorgensen, Esben et al. (2012) Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA 307:391-7
Needham, Larry L; Grandjean, Philippe; Heinzow, Birger et al. (2011) Partition of environmental chemicals between maternal and fetal blood and tissues. Environ Sci Technol 45:1121-6
Audouze, Karine; Grandjean, Philippe (2011) Application of computational systems biology to explore environmental toxicity hazards. Environ Health Perspect 119:1754-9
Grandjean, Philippe; Poulsen, Lars K; Heilmann, Carsten et al. (2010) Allergy and sensitization during childhood associated with prenatal and lactational exposure to marine pollutants. Environ Health Perspect 118:1429-33

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