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Semedo, Filipa Alexandra de Matos Tavares
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- House dust mite molecular sensitisation profile and allergic respiratory disease expressionPublication . Semedo, Filipa Alexandra de Matos Tavares; Inácio, Filipe Fernando da Cruz; Barata, Luís Manuel TabordaBackground The molecular era of allergology has transformed our understanding of IgE sensitisation, enabling precise identification of allergen components through component-resolved diagnostics (CRD). House dust mite (HDM) and storage mite (SM) allergens are major drivers of allergic asthma (AA) and allergic rhinitis (AR), yet their individual contributions to clinical expression and evolution of disease remain incompletely understood. Objectives This thesis aimed to characterise the clinical relevance of individual mite molecular components in allergic respiratory diseases by combining high-level evidence synthesis, in vivo functional assessment, and real-world cross-sectional and longitudinal analysis. Methods A systematic review and meta-analysis (SR/MA) of 101 studies (n = 23 781) was conducted to assess the relationship between sensitisation to major HDM and SM components and clinical phenotypes. The clinical impact of newly identified major allergen Der p 23 was assessed trough monosensitisation to this allergen in allergic respiratory patients with no other sensitisations. Functional relevance of SM Lepidoglyphus destructor (Lep d) was investigated using nasal provocation testing (NPT) with Lep d in urban, non-occupational patients. The clinical impact of Lep d was also analised through monosensitisation to Lep d 2 in allergic respiratory patients. Lastly, a 20-year longitudinal cohort study compared the evolution of mite molecular sensitisation profiles and respiratory symptom dynamics in adult population and comparison with children and adolescent cohorts. Results The SR/MA revealed that major mite allergens as Der p 1, Der p 2, Der p 23, Der f 1, Der f 2, Lep d 2 and Blo t 5 have higher sensitisation rates and sIgE concentrations in patients with AA than in those with only AR. In vivo testing with NPT and Lep d 2 monosensitisation confirmed that Lep d is clinically relevant in urban settings in patients with allergic respiratory disease. Monosensitisation to Der p 23 showed potential clinical impact, highlighting overlooked profiles in routine diagnosis. The longitudinal study demonstrated molecular involution in adults—marked by declining sIgE responses and improved clinical outcomes—contrasting with molecular spreading in the paediatric cohort. This decline was independent of allergen immunotherapy (AIT) and may reflect immunosenescence or age-related immune modulation. Conclusions This thesis establishes new evidence linking mite molecular sensitisation patterns with clinical expression, severity, and disease evolution in AA and AR. It underscores the clinical utility of CRD for both diagnosis and prognosis and supports the need for artificial-intelligence guided stratification and development of component-based AIT in future personalised allergy care.