Prenatal origins of allergic disease,☆☆,

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Abstract

The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Because genetic stock has not changed, environmental factors must have influenced the phenotype. Infants who experience the development of allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite and birch pollen in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least 1 atopic parent with asthma, who experienced the development of allergic symptoms and positive skin prick test by 1 year of age had raised proliferative responses to house dust mite at birth compared with those infants with no symptoms. In genetically predisposed individuals, antenatal factors including maternal and thereby fetal exposure to allergens and materno-placental-fetal immunologic interactions are active in determining whether an allergic predisposition is manifested as disease. (J Allergy Clin Immunol 2000;105:S493-6.)

Section snippets

ALTERED IMMUNE RESPONSES AT BIRTH

There is a distinct need to further elucidate the factors that lead to the early development of immune responses associated with an increased risk of the development of allergic disease. It is often difficult to separate the effect of environmental conditions occurring during pregnancy from those in existence during the first months of life because they are rarely significantly different. An obvious example is cigarette smoking. Most mothers who smoke during pregnancy will continue to do so

FURTHER INVESTIGATIONS

We are currently investigating the presence of mRNA coding for IFN-γ, IL-4, IL-5, IL-10, IL-12, and IL-13 and their protein products in the fetal-placental-maternal human system in the second and third trimesters of pregnancy to determine how, and when, maternal and placental cellular responses affect the development and control of infant responses to allergens. We have preliminary evidence of CD68+ monocytes in both the maternal and fetal circulations within the placenta, indicating active

CONCLUSIONS AND HYPOTHESES

The intrauterine environment in which a fetus develops is highly biased toward TH2-like immune responses. The systems of babies with an inherited tendency toward a deficient production of IFN-γ are less likely to be able to counteract the effect of this imbalance on their own developing immune responses, particularly if the mother is also allergic and is exposed to the allergens that trigger her own allergic disease during the pregnancy. This may cause a further increase in the concentrations

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    Supported by The National Asthma Campaign, The British Lung Foundation, The David and Frederick Barclay Foundation, The British Allergy Foundation, The European Society for Pediatric Allergy and Immunology, Sandoz Pharmaceuticals, Pharmacia, and National Power.

    ☆☆

    Reprint requests: Jill Warner, PhD, University Child Health, Level G Centre Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD United Kingdom.

    0091-6749/2000 $12.00 + 0  1/0/100088

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