Allergic rhinitis is a local disease: the role of local IgE production, basophils and mast cells

The introduction to this thesis summarizes the literature which indicates that there is a discrepancy between sensitisation and allergic disease. Two aspects which might play a role in this discrepancy are the differences between production and funtion of local versus systemic lgE and the differences in mast cell and basophil function in the blood compared to in the tissues. Mast cells, basophils and IgE are key players in the allergic inflammation. The aim of the studies described in this thesis was to focus on these differences between local and systemic function of these key factors. The research questions addressed in this thesis are: Mast cells and basophils seem to play an important role in the pathogenesis of allergic rhinitis. Do the phenotypes of mast cells and basophilic cells changed by allergen provocation in the nasal mucosa of allergic rhinitis patients (Chapter 3)? The developmental relationship bet\veen mast cells and basophils has not yet been totally resolved. What is the relation bet\veen basophil progenitors, mast cell progenitors, basophils and mast cells in the circulation and in the nasal mucosa (Chapter 3)? Allergic mucosa inflammation is regulated by the local production and release of several Th2 cytokines. Which increase in cytokines and chemokines is correlated to inflammatory cells and symptomatology of the patient? What is the time line of the various cytokines and chemokines after allergen provocation (Chapter 4)? Is it possible to develop a method to detect specific lgE in tissues. Does production of specific IgE take place locally in the nasal mucosa (Chapter 5)? Where do basophils and mast-cell of allergic rhinitis patients acquire IgE (Chapter 5)? To adress these questions multiple blood samples and biopsies of the nasal mucosa of allergic patients were taken before, during and after allergen provocation. Cellular infiltrates in these biopsies were compared to those in biopsies of normal controls. Cell phenotypes, production and release of mediators and cytokines were studied using immunohistochemical techniques and in situ hybridisation.