Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.

BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.

Allergic disease and atopic sensitization in children in relation to measles vaccination and measles infection.

OBJECTIVE: Our aim was to investigate the role of measles vaccination and measles infection in the development of allergic disease and atopic sensitization. METHODS: A total of 14 893 children were included from the cross-sectional, multicenter Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study, conducted in 5 European countries (Austria, Germany, the Netherlands, Sweden, and Switzerland). The children were between 5 and 13 years of age and represented farm children, Steiner-school children, and 2 reference groups. Children attending Steiner schools often have an anthroposophic (holistic) lifestyle in which some immunizations are avoided or postponed. Parental questionnaires provided information on exposure and lifestyle factors as well as symptoms and diagnoses in the children. A sample of the children was invited for additional tests, and 4049 children provided a blood sample for immunoglobulin E analyses. Only children with complete information on measles vaccination and infection were included in the analyses (84%). RESULTS: In the whole group of children, atopic sensitization was inversely associated with measles infection, and a similar tendency was seen for measles vaccination. To reduce risks of disease-related modification of exposure, children who reported symptoms of wheezing and/or eczema debuting during first year of life were excluded from some analyses. After this exclusion, inverse associations were observed between measles infection and "any allergic symptom" and "any diagnosis of allergy by a physician." However, no associations were found between measles vaccination and allergic disease. CONCLUSION: Our data suggest that measles infection may protect against allergic disease in children.

Allergic disease and sensitization in Steiner school children.

BACKGROUND: The anthroposophic lifestyle has several features of interest in relation to allergy: for example, a restrictive use of antibiotics and certain vaccinations. In a previous Swedish study, Steiner school children (who often have an anthroposophic lifestyle) showed a reduced risk of atopy, but specific protective factors could not be identified. OBJECTIVE: To investigate factors that may contribute to the lower risk of allergy among Steiner school children. METHODS: Cross-sectional multicenter study including 6630 children age 5 to 13 years (4606 from Steiner schools and 2024 from reference schools) in 5 European countries. RESULTS: The prevalence of several studied outcomes was lower in Steiner school children than in the reference group. Overall, there were statistically significant reduced risks for rhinoconjunctivitis, atopic eczema, and atopic sensitization (allergen-specific IgE > or =0.35 kU/L), with some heterogeneity between the countries. Focusing on doctor-diagnosed disease, use of antibiotics during first year of life was associated with increased risks of rhinoconjunctivitis (odds ratio [OR], 1.97; 95% CI, 1.26-3.08), asthma (OR, 2.79; 95% CI, 2.03-3.83), and atopic eczema (OR, 1.63; 95% CI, 1.22-2.17). Early use of antipyretics was related to an increased risk of asthma (OR, 1.54; 95% CI, 1.11-2.13) and atopic eczema (OR, 1.32; 95% CI, 1.02-1.71). Children having received measles, mumps, and rubella vaccination showed an increased risk of rhinoconjunctivitis, whereas measles infection was associated with a lower risk of IgE-mediated eczema. CONCLUSION: Certain features of the anthroposophic lifestyle, such as restrictive use of antibiotics and antipyretics, are associated with a reduced risk of allergic disease in children.