Parental smoking impairs vaccine responses in children with atopic genotypes

G.S. Baynam, S.K. Khoo, J. Rowe, G. Zhang, I.A. Laing, C.M. Hayden, Merci Kusel, Nicholas De Klerk, Peter Sly, J. Goldblatt, Patrick Holt, P.N. Le Souef

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Abstract

Background: Gene-environment interactions play central roles in controlling postnatal maturation of immune function, but their effects on infant vaccine responses are unknown. Genetic variants associated with atopy and the environmental factor of exposure to parental smoking (PS) of tobacco independently alter immune responses.Objective: We sought to investigate the hypothesis that genetic variants associated with atopy and their interaction with PS influence infant vaccine responsiveness.Methods: In 200 infants with parental atopic history, relationships were sought between polymorphisms in the IL-4, IL-4 receptor alpha (IL-4R alpha), and IL-13 genes; PS; and immune responses to diphtheria/tetanus vaccination.Results: Analyses stratified by PS unmasked negative associations between atopic alleles of these genes and vaccine outcomes. The most consistent involved the IL-4R alpha 551 QR/QQ genotypes, which were associated with reduced IgG levels (P = .02) and T-cell responses (IFN-gamma, P = .002; IL-10, P = .01; IL-13, P = .01; IL-5, P = .06) to tetanus toxoid and parallel reductions in polyclonal T-cell responses and innate immune responses in PS-exposed infants.Conclusion: PS potentiates suppressive effects of variants in immune response genes in children. These effects are not observed in the absence of this exposure. Ultimately, this finding might have implications for infant vaccination in countries with high smoking rates. It might also have broader implications in relation to environmental toxicology because it demonstrates specific mechanisms through which the developing immune system might be differentially sensitive to low-level toxicant exposures.Clinical implications: PS interacts with genes associated with atopy to impair vaccine responses. These interactions might have vaccine design and public health implications.
Original languageEnglish
Pages (from-to)366-374
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number2
DOIs
Publication statusPublished - 2007

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Baynam, G. S., Khoo, S. K., Rowe, J., Zhang, G., Laing, I. A., Hayden, C. M., ... Le Souef, P. N. (2007). Parental smoking impairs vaccine responses in children with atopic genotypes. Journal of Allergy and Clinical Immunology, 119(2), 366-374. https://doi.org/10.1016/j.jaci.2006.09.018