Local IgE in non-atopic asthma : evidence and role of a specific IgE response to mite allergens

(eng) This work focuses on non-allergic (so-called ‘intrinsic’) asthma. The central hypothesis of this thesis is that intrinsic asthma might be driven by a local allergic reaction. A phenomenon that has been, so far, only described in the nose, under the concept of ‘entopy’. In the first part of this work, we confirmed that intrinsic asthma shares some immunopathological similarities with allergic asthma. In particular, the level of airways IgE production was similar between both phenotypes and can occur independently of a systemic production. Surprisingly, at least a part of this IgE is specific to Der p house dust mite allergens. However, in intrinsic asthmatic, lung exposure to the allergen did not translate into immediate (or late) allergic reaction. Looking at basophils from intrinsic asthma patients, as a model of immediate allergic reaction, suggested that these cells were less prone to activate upon IgE stimulation. We therefore postulated that a second signal was required in intrinsic asthma to promote the IgE-FcERI pathway, which seems constitutively primed in atopic asthma. In the second study, we studied the blood basophils and their signaling machinery, with the hypothesis that basophils from intrinsic asthmatics could be less reactive to IgE than basophils from allergic patients and focusing on Syk tyrosine kinase as critical intracellular signal conditioning IgE responsiveness. We have assessed here the expression of two important surface markers of basophils activation, namely CD203c and CD63, and confirmed difference in the reactivity of basophils from intrinsic asthma vs atopic asthmatics. This finding was associated with a lower expression of Syk in intrinsic asthma, one of the pivotal kinase involved in the signal transduction of FcERI. These two original studies shed new insights into the immunopathological pathways involved in intrinsic asthma, and reinforce the belief that local IgE production has a role to play in some non-allergic asthmatics