Nasal upregulation of CST1 in dog sensitised children with severe allergic airway disease

Background The clinical presentation of children sensitised to dog dander varies from asymptomatic to severe allergic airway disease, but the genetic mechanisms underlying these differences are not clear.

Objective To investigate nasal transcriptomic profiles associated with dog dander sensitisation in school children and to reveal clinical symptoms related with these profiles.

Methods RNA was extracted from nasal epithelial cell brushings of children sensitised to dog dander and healthy controls. Blood sample analyses included IgE against dog dander, dog allergen molecules, other airborne and food allergens, basophil activation and white blood cell counts. Clinical history of asthma and rhinitis was recorded, and lung function was assessed (spirometry, methacholine provocation and FeNO).

Results The most over-expressed gene in children sensitised to dog dander compared to healthy controls was CST1, coding for Cystatin 1. A cluster of these children with enhanced CST1 expression showed lower FEV1, increased bronchial hyper-reactivity, pronounced eosinophilia and higher basophil allergen threshold sensitivity compared with other children sensitised to dog dander. Multi-sensitisation to lipocalins was also more common in this group.

Conclusions Over-expression of CST1 is associated with more severe allergic airway disease in children sensitised to dog dander. CST1 is thus a possible biomarker of the severity of allergic airway disease and a possible therapeutic target for the future treatment of airborne allergy.