Effects of established allergen sensitization on immune and airway responses after secondary allergen sensitization

BackgroundSpreading of sensitization with clinical manifestation of allergy is often observed in atopic individuals.ObjectiveTo investigate the effects of an established primary allergen sensitization on immune responses and airway inflammation/reactivity on secondary allergen sensitization and airway challenges in a murine model.MethodsBalb/c mice were primarily sensitized intraperitoneally with ovalbumin or PBS, followed by systemic sensitization and airway challenges with latex extract as a secondary, unrelated allergen. Purely sham-sensitized animals were included as controls. In a second set of experiments, the primary and secondary allergens were switched.ResultsSensitization with ovalbumin before sensitization with latex resulted in increased production of total and latex-specific (Hev b 3–specific) IgE and IgG1, and enhanced secretion of TH2-cytokines by spleen mononuclear cells cultured with mitogen compared with single latex-sensitized mice. Furthermore, airway challenges of double-sensitized mice (ovalbumin + latex) with latex caused a significant increase in airway reactivity compared with purely latex-sensitized and challenged animals. These effects were dependent on dosing and timing of the primary sensitization in relation to the secondary sensitization and independent of the primary allergen used.ConclusionPrimary sensitization boosted systemic TH2 immune responses and enhanced the development of airway reactivity after sensitization and airway challenges with a secondary, unrelated allergen. This effect of consecutive priming was dependent on the strength of the primary sensitization but independent of the allergen used. The results explain the increased susceptibility toward sensitization spreading in atopic individuals.Clinical implicationsBecause sensitization spreading is facilitated by primary sensitization, early prevention measurements or immunotherapy should be considered at this stage of monosensitization.