Development of IgG subclass antibodies to allergens in early childhood

• Background: Immune responses to allergens in young children include both Thl and Th2 like immunity, which may regulate the secretion of IgG subclass antibodies differently. The time, route and level of exposure to an allergen, as well as maternally transferred immunity, may be decisive whether sensitisation or tolerance will ensue. To study this, we established sensitive methods and investigated the development of IgG subclass antibodies to food and inhalant allergens during childhood.Material and Methods: The study group comprised a cohort of 96 children participating in a prospective study. IgG subclass antibodies to ß-lactoglobulin, ovalbumin, Bet v 1 and cat dander were analysed at birth, 6 and 18 months and 8 years by ELISA. At 8 years of age, PBMC from 55 of the children were stimulated with birch and ß-lactoglobulin. Production of IL-5, IL-6, IL-10, IL-13 and IFN-y was analysed by ELISA and expression of IL-4 and IL-9 mRNA by semiquantitative RTPCR.Results: High cord blood levels of IgG antibodies to inhalant, but not to food, allergens were associated with less development of atopy in the children during the first eight years of life. IgG subclass antibody responses to allergens were commonly detected during childhood and were largely restricted to the IgG1 subclass. The production of this opsonising and complement activating subclass was associated with Thllike immunity at 8 years of age. IgG subclass antibodies to food allergens peaked in infancy, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increased with age. Exposure to cow's milk during the first three months of life was associated with high IgG subclass antibodies to ß-lactoglobulin up to eight years. Exposure to cat and birch tended to be associated with high antibody levels to those allergens, whereas antibody levels to ovalbumin were not related to the introduction of egg in the diet. Atopic symptoms and the presence of positive skin prick tests and circulating IgE antibodies to allergens were associated with high levels of IgG subclass, especially Th2 associated IgG4, antibody responses to allergens. For the food allergens, the differences were mostly marked early in life. Birch induced IL-4 expression may be the major factor determining IgE antibody formation to that allergen, while allergen induced IL-5, IL-6 and IL-10 secretion in PBMC was associated with atopic symptoms.Conclusions: Maternally derived antibodies may modulate immune responses. The tolerance-inducing mechanisms in the intestinal mucosa may be less effective during the first months of life. Responses to food and inhalant allergens show different kinetics. Thl like associated IgG1 antibodies to allergens are commonly observed in both atopic and non-atopic children, whereas Th2 like associated IgG4 responses are more atopy dependent.

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