Ulrika Käck1,2, Elisabet Einarsdottir3,4,5, Marianne van Hage6, Anna Asarnoj7,8, Anna James9, Anna Nopp1,2, Kaarel Krjutškov3,10,11, Shintaro Katayama3,5,12, Juha Kere3,13, Gunnar Lilja1,2, Cilla Söderhäll3,7,8,14, Jon R Konradsen7,8,14. 1. Dept of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. 2. Sach's Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden. 3. Dept of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. 4. Science for Life Laboratory, Department of Gene Technology, KTH-Royal Institute of Technology, Solna, Sweden. 5. Folkhälsan Research Center, Helsinki, Finland. 6. Dept of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 7. Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 8. Dept of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 9. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 10. Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia. 11. Competence Centre on Health Technologies, Tartu, Estonia. 12. University of Helsinki, Stem Cells and Metabolism Research Program, Helsinki, Finland. 13. Folkhälsan Research Institute, and Stem Cell and Metabolism Research Program, University of Helsinki, Helsinki, Finland. 14. These authors contributed equally.
Abstract
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.
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.
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