Antigens Drive Memory IgE Responses in Human Allergy via the Nasal Mucosa

BACKGROUND: Natural allergen contact induces an increase of IgE levels and sensitivity but the mechanisms underlying the allergen-specific memory responses are poorly understood. Furthermore, it has not been studied whether allergen exposure affects the molecular reactivity profiles in patients. The aim of this study was to analyze the influence of nasal allergen encounter on the molecular profile and magnitude of memory IgE responses and on systemic sensitivity. METHODS: We investigated allergen-specific IgE, IgG subclass and IgM responses to defined allergen molecules (grass pollen: Phl p 1, Phl p 2 and Phl p 5; birch pollen: Bet v 1 and Bet v 2) in allergic patients in response to natural as well as to controlled nasal and dermal allergen exposure. Changes in systemic sensitivity were monitored by skin prick testing and by basophil histamine release experiments. RESULTS: Respiratory antigen exposure boosted IgE levels to a pre-established profile of allergen molecules without inducing significant IgM responses or new IgE specificities in allergic individuals. The importance of the route of allergen contact is demonstrated by an increase of systemic IgE levels and sensitivity after nasal exposure. In vitro sensitisation of basophils with pre- and post-seasonal serum samples suggests an allergen-induced elevation of specific IgE as a cause for the increased allergen-specific sensitivity. CONCLUSION: The characteristics of the allergen-driven antibody responses indicate a direct activation of an established pool of IgE memory cells with defined specificities as an underlying mechanism. Our finding that nasal allergen contact is a major factor for the boosting of memory IgE and systemic sensitivity may open new therapeutic possibilities.