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

J Allergy Clin Immunol. 2020 Sep;146(3):583-594.e6. doi: 10.1016/j.jaci.2020.02.037. Epub 2020 Apr 6.


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.

Keywords: Allergic rhinitis; biomarkers; chemokines; cytokines; immunoglobulins; nasal symptoms; pollen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology*
  • Antigens, Plant / immunology*
  • Biomarkers
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interleukin-33 / immunology
  • Interleukin-8 / immunology
  • Male
  • Middle Aged
  • Nasal Mucosa / immunology
  • Pollen / immunology*
  • Rhinitis, Allergic, Seasonal / blood
  • Rhinitis, Allergic, Seasonal / immunology*
  • Seasons
  • Young Adult


  • Allergens
  • Antigens, Plant
  • Biomarkers
  • CXCL8 protein, human
  • IL33 protein, human
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-33
  • Interleukin-8
  • Bet v 1 allergen, Betula
  • Immunoglobulin E