Background. It has been established that T cell responses of foetal origin to inhalant allergens are present in most cord blood samples. These immune responses could possibly be explained by transplacental passage of peptides, either as free antigens or in complexes with IgG, providing the foetus with a trigger for the priming of the T cell system already in utero. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is unknown. IgA antibodies to inhalant allergens have not been previously detected in human milk.
Objective. The aim of this thesis was to explore whether inhaled allergens in serum and IgA antibodies in breast milk could contribute to the allergic immune responses to allergens in the children.
Methods. The presence of cat allergen Fel d 1 was analysed by ELISA in serum samples from cat allergic asthmatic children. To detect IgG immune complexes (IC), affmity chromatography purification and Western blotting were performed. Iri:nnune complexes with Fel d 1-IgE were detected by a modification of MagicLite, and their specificity was assessed by different approaches. Serum samples from allergic and non-allergic mothers, and cord blood from their infants, were measured for the presence of Fel d 1-IgG immune complexes by an amplified ELISA. Cord blood mononuclear cells (CBMC) of babies from allergic and non-allergic mothers were stimulated with cat allergen and the production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA and the levels related to the presence of IC. Furthermore, IgG1 and IgG4 antibodies to cat were measured by ELISA. Colostrum and samples of mature milk from allergic and non-allergic mothers were analysed for IgA antibodies to cat, P-lactoblobulin (BLG) and ovalbumin (OVA) by an amplified ELISA.
Results. The cat allergen Fel d I was detected in 70% of sera from cat allergic chilch'en, but not in any of the controls. The allergen was present in complexes with IgE and IgG antibodies as corroborated by different approaches. Immune complexes with IgG were detected in sera from allergic and non-allergic mothers, as well as in the cord blood from their babies, but neither the prevalence nor the levels of complexes were related to maternal allergy. This was also the case for IgG antibodies to cat. The production of IL-5, IL-10, IL-13 and IFN-γ by CBMC was not influenced by maternal atopy. Interferon-y secretion by CBMC after stimulation with cat allergen, however, was less conunonly detected in samples with immune complexes. Secretory IgA to cat and OVA allergens were frequently detected in colostrum and mature milk, while antibodies to BLG were less common. The antibody levels to cat and BLG were similar in allergic and non-allergic mothers.
Conclusion. The presence of IC with allergens may contribute to maintaining immune responsiveness and sensitivity in allergic individuals. Low levels of transplacentally transferred IC can conceivable provide the foetus with the signal for priming ofT cell responses to inhalant allergens. This seems to be a nonnal mechanism, as the immune responses are not related to maternal allergy. Low level exposure of the maternal mucosa, e.g. by inhalant allergens, can induce IgA antibody secretion in breast milk, but this mechanism is not related with any protective effect against allergy.
Linköping: Linköpings universitet , 2001. , 111 p.
2001-10-19, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)