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

  1. Ulrika Käck1,2,
  2. Elisabet Einarsdottir3,4,5,
  3. Marianne van Hage6,
  4. Anna Asarnoj7,8,
  5. Anna James9,
  6. Anna Nopp1,2,
  7. Kaarel Krjutskov3,10,11,
  8. Shintaro Katayama3,5,12,
  9. Juha Kere3,13,
  10. Gunnar Lilja1,2,
  11. Cilla Söderhäll3,7,8,14⇑ and
  12. Jon R. Konradsen7,8,14
  1. 1Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
  2. 2Sachś Childrens and Youth Hospital, Södersjukhuset, Stockholm, Stockholm, Sweden
  3. 3Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
  4. 4Science for Life Laboratory, Department of Gene Technology, KTH-Royal Institute of Technology, Solna, Sweden
  5. 5Folkhälsan Research Center, Helsinki, Finland
  6. 6Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
  7. 7Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
  8. 8Department of Womeńs and Children's Health, Karolinska Institutet, Stockholm, Sweden
  9. 9Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  10. 10Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia
  11. 11Competence Centre on Health Technologies, Tartu, Estonia
  12. 12University of Helsinki, Stem Cells and Metabolism Research Program, Helsinki, Finland
  13. 13Folkhälsan Research Institute, and Stem Cell and Metabolism Research Program, University of Helsinki, Helsinki, Finland
  14. 14shared last authorship
  1. Cilla Söderhäll, Karolinska Institutet, Department of Women's and Children's health, BioClinicum J9:30, Visionsgatan 4, SE-171 76 Stockholm, Sweden. E-mail: cilla.soderhall{at}ki.se

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.

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.

Footnotes

This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.

Conflict of interest: U. Käck reports a lecture fee from Thermo Fisher outside the submitted work.

Conflict of interest: Dr. 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: Dr. Asarnoj has nothing to disclose.

Conflict of interest: Dr. James has nothing to disclose.

Conflict of interest: Dr. Nopp has nothing to disclose.

Conflict of interest: Dr. Krjutškov has nothing to disclose.

Conflict of interest: Dr. Katayama reports grants from Jane and Aatos Erkko Foundation, during the conduct of the study.

Conflict of interest: Dr. Kere has nothing to disclose.

Conflict of interest: Dr. Lilja has nothing to disclose.

Conflict of interest: Dr. Söderhäll has nothing to disclose.

Conflict of interest: Dr. Konradsen has received material from Thermo Fishes Scientific to perform IgE analysis in this project.

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  • Received December 7, 2020.
  • Accepted January 27, 2021.
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