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. The objective of the present study was 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 exhaled nitric oxide fraction).
Results: The most overexpressed 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 forced expiratory volume in 1 s, increased bronchial hyperreactivity, pronounced eosinophilia and higher basophil allergen threshold sensitivity compared with other children sensitised to dog dander. In addition, multi-sensitisation to lipocalins was more common in this group.
Conclusions: Overexpression 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.
Competing Interests: Conflict of interest: U. Käck reports a lecture fee from Thermo Fisher outside the submitted work. Conflict of interest: E. Einarsdottir has nothing to disclose. Conflict of interest: M. van Hage reports lecture fees from Thermo Fisher Scientific and ALK, and consultancy fees from Biomay AG, Vienna, Austria and Hycor Biomedical LLC, CA, US, outside the submitted work. Conflict of interest: A. Asarnoj has nothing to disclose. Conflict of interest: A. James has nothing to disclose. Conflict of interest: A. Nopp has nothing to disclose. Conflict of interest: K. Krjutškov has nothing to disclose. Conflict of interest: S. Katayama reports grants from the Jane and Aatos Erkko Foundation during the conduct of the study. Conflict of interest: J. Kere has nothing to disclose. Conflict of interest: G. Lilja has nothing to disclose. Conflict of interest: C. Söderhäll has nothing to disclose. Conflict of interest: J.R. Konradsen has received material from Thermo Fisher Scientific to perform IgE analysis in this project.
(Copyright ©The authors 2021. This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.)