Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure

Mehmet Gökkaya, Athanasios Damialis, Thomas Nussbaumer, Isabelle Beck, Nikolaos Bounas-Pyrros, Sebastian Bezold, Marie M. Amisi, Franziska Kolek, Antonia Todorova, Adam Chaker, Lorenz Aglas, Fatima Ferreira, Frank A. Redegeld, Jens O. Brunner, Avidan U. Neumann, Claudia Traidl-Hoffmann, Stefanie Gilles

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: Pollen exposure induces local and systemic allergic immune responses in sensitized individuals, but nonsensitized individuals also are exposed to pollen. The kinetics of symptom expression under natural pollen exposure have never been systematically studied, especially in subjects without allergy. Objective: We monitored the humoral immune response under natural pollen exposure to potentially uncover nasal biomarkers for in-season symptom severity and identify protective factors. Methods: We compared humoral immune response kinetics in a panel study of subjects with seasonal allergic rhinitis (SAR) and subjects without allergy and tested for cross-sectional and interseasonal differences in levels of serum and nasal, total, and Betula verrucosa 1–specific immunoglobulin isotypes; immunoglobulin free light chains; cytokines; and chemokines. Nonsupervised principal component analysis was performed for all nasal immune variables, and single immune variables were correlated with in-season symptom severity by Spearman test. Results: Symptoms followed airborne pollen concentrations in subjects with SAR, with a time lag between 0 and 13 days depending on the pollen type. Of the 7 subjects with nonallergy, 4 also exhibited in-season symptoms whereas 3 did not. Cumulative symptoms in those without allergy were lower than in those with SAR but followed the pollen exposure with similar kinetics. Nasal eotaxin-2, CCL22/MDC, and monocyte chemoattactant protein-1 (MCP-1) levels were higher in subjects with SAR, whereas IL-8 levels were higher in subjects without allergy. Principal component analysis and Spearman correlations identified nasal levels of IL-8, IL-33, and Betula verrucosa 1–specific IgG4 (sIgG4) and Betula verrucosa 1–specific IgE (sIgE) antibodies as predictive for seasonal symptom severity. Conclusions: Nasal pollen–specific IgA and IgG isotypes are potentially protective within the humoral compartment. Nasal levels of IL-8, IL-33, sIgG4 and sIgE could be predictive biomarkers for pollen-specific symptom expression, irrespective of atopy.

Original languageEnglish
Pages (from-to)583-594.e6
JournalJournal of Allergy and Clinical Immunology
Issue number3
StatePublished - Sep 2020
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the Christine Kühne - Center for Allergy Research and Education (CK-CARE); The Initiative and Networking Fund of the Helmholtz Association (Immunology & Inflammation).

Funding Information:
We thank Kristina Beresowski for technical assistance. This research was partly implemented within the framework of the EU-COST Action ADOPT (New Approaches in Detection of Pathogens and Aeroallergens), under grant CA18226 ( EU Framework Program Horizon 2020 ).

Publisher Copyright:
© 2020


  • Allergic rhinitis
  • biomarkers
  • chemokines
  • cytokines
  • immunoglobulins
  • nasal symptoms
  • pollen


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