Immunoglobulin G4-antibodies to rBet v 1 and risk of sensitization and atopic disease in the child

BACKGROUND: In 1993 extremely high levels of birch-pollen were recorded in Stockholm, Sweden. This provided an opportunity to evaluate the effects of aeroallergen exposure (exp.) on the early immune response. OBJECTIVE: To assess the influence of exp. to birch-pollen during pregnancy and infancy on the allergen-specific IgE- and IgG4-antibody (ab) response and the development of atopic disease in children. METHODS: A total of 970 children with atopic heredity and born in Stockholm 1992, 1993 or 1994 were investigated at age 4.5-5 years. They were divided into five groups; high-dose exp. at 1 year of age, high-dose exp. at 0-3 months, low-dose exp. at 0-3 months, high-dose exp. during pregnancy and low-dose exp. during pregnancy. The children were examined and skin prick tested with inhalant and food allergens. IgE abs (against birch-pollen and recombinant Bet v 1(rBet v1)) and IgG4 abs (against rBet v 1) were analysed in serum. All children were assembled in one group to assess the effects of different ab responses (IgE/IgG4) on the development of atopic disease. RESULTS: Children exposed to high doses of birch-pollen during the first 3 months of life more often had detectable levels of IgG4 abs to rBet v 1 than the children in the other groups (P < 0.001), independent of sensitization to birch. Overall, the risk of allergic rhinoconjunctivitis was increased among children sensitized to birch-pollen and appeared more pronounced in children without detectable levels of IgG4 ab to rBet v 1 (Odds ratio 9.4; 95% Confidence interval: 5.5-16.1). IgE sensitization to birch-pollen seemed to have a stronger influence on the development of atopic disease than the IgG4-ab response. CONCLUSION: Exposure to high doses of inhalant allergens during the early postnatal period is associated with detectable levels of allergen-specific IgG4 ab even at 5 years of age. An immune modulating effect by IgG4 on symptoms of allergic rhinoconjunctivitis is suggested in children sensitized to birch.