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

doi:10.1016/j.jaci.2020.02.037

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 journal › Article › peer-review

18 Scopus citations

Abstract

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 language	English
Pages (from-to)	583-594.e6
Journal	Journal of Allergy and Clinical Immunology
Volume	146
Issue number	3
DOIs	https://doi.org/10.1016/j.jaci.2020.02.037
State	Published - Sep 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020

Funding

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

Funders	Funder number
EU-COST
New Approaches in Detection of Pathogens and Aeroallergens	CA18226
Helmholtz Association
Christine Kühne – Center for Allergy Research and Education

Keywords

Allergic rhinitis
biomarkers
chemokines
cytokines
immunoglobulins
nasal symptoms
pollen

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10.1016/j.jaci.2020.02.037

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Gökkaya, M., Damialis, A., Nussbaumer, T., Beck, I., Bounas-Pyrros, N., Bezold, S., Amisi, M. M., Kolek, F., Todorova, A., Chaker, A., Aglas, L., Ferreira, F., Redegeld, F. A., Brunner, J. O., Neumann, A. U., Traidl-Hoffmann, C., & Gilles, S. (2020). Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure. Journal of Allergy and Clinical Immunology, 146(3), 583-594.e6. https://doi.org/10.1016/j.jaci.2020.02.037

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abstract = "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",

author = "Mehmet G{\"o}kkaya and Athanasios Damialis and Thomas Nussbaumer and Isabelle Beck and Nikolaos Bounas-Pyrros and Sebastian Bezold and Amisi, {Marie M.} and Franziska Kolek and Antonia Todorova and Adam Chaker and Lorenz Aglas and Fatima Ferreira and Redegeld, {Frank A.} and Brunner, {Jens O.} and Neumann, {Avidan U.} and Claudia Traidl-Hoffmann and Stefanie Gilles",

note = "Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = sep,

doi = "10.1016/j.jaci.2020.02.037",

language = "אנגלית",

volume = "146",

pages = "583--594.e6",

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Gökkaya, M, Damialis, A, Nussbaumer, T, Beck, I, Bounas-Pyrros, N, Bezold, S, Amisi, MM, Kolek, F, Todorova, A, Chaker, A, Aglas, L, Ferreira, F, Redegeld, FA, Brunner, JO, Neumann, AU, Traidl-Hoffmann, C & Gilles, S 2020, 'Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure', Journal of Allergy and Clinical Immunology, vol. 146, no. 3, pp. 583-594.e6. https://doi.org/10.1016/j.jaci.2020.02.037

TY - JOUR

T1 - Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure

AU - Gökkaya, Mehmet

AU - Damialis, Athanasios

AU - Nussbaumer, Thomas

AU - Beck, Isabelle

AU - Bounas-Pyrros, Nikolaos

AU - Bezold, Sebastian

AU - Amisi, Marie M.

AU - Kolek, Franziska

AU - Todorova, Antonia

AU - Chaker, Adam

AU - Aglas, Lorenz

AU - Ferreira, Fatima

AU - Redegeld, Frank A.

AU - Brunner, Jens O.

AU - Neumann, Avidan U.

AU - Traidl-Hoffmann, Claudia

AU - Gilles, Stefanie

PY - 2020/9

Y1 - 2020/9

N2 - 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.

AB - 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.

KW - Allergic rhinitis

KW - biomarkers

KW - chemokines

KW - cytokines

KW - immunoglobulins

KW - nasal symptoms

KW - pollen

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U2 - 10.1016/j.jaci.2020.02.037

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SN - 0091-6749

VL - 146

SP - 583-594.e6

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -

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

Abstract

Bibliographical note

Funding

Keywords

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