PMID- 32272131 OWN - NLM STAT- MEDLINE DCOM- 20210310 LR - 20210310 IS - 1097-6825 (Electronic) IS - 0091-6749 (Linking) VI - 146 IP - 3 DP - 2020 Sep TI - Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure. PG - 583-594.e6 LID - S0091-6749(20)30419-X [pii] LID - 10.1016/j.jaci.2020.02.037 [doi] 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 IgG(4) (sIgG(4)) 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, sIgG(4) and sIgE could be predictive biomarkers for pollen-specific symptom expression, irrespective of atopy. CI - Copyright (c) 2020. Published by Elsevier Inc. FAU - Gokkaya, Mehmet AU - Gokkaya M AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. FAU - Damialis, Athanasios AU - Damialis A AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. FAU - Nussbaumer, Thomas AU - Nussbaumer T AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. FAU - Beck, Isabelle AU - Beck I AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. FAU - Bounas-Pyrros, Nikolaos AU - Bounas-Pyrros N AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany; Department of Dermatology, University Clinic Augsburg, Augsburg, Germany. FAU - Bezold, Sebastian AU - Bezold S AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany; Department of Dermatology, University Clinic Augsburg, Augsburg, Germany. FAU - Amisi, Marie M AU - Amisi MM AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. FAU - Kolek, Franziska AU - Kolek F AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. FAU - Todorova, Antonia AU - Todorova A AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany; Department of Dermatology, University Clinic Augsburg, Augsburg, Germany. FAU - Chaker, Adam AU - Chaker A AD - ENT Department, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. FAU - Aglas, Lorenz AU - Aglas L AD - Department of Molecular Biology, University of Salzburg, Salzburg, Austria. FAU - Ferreira, Fatima AU - Ferreira F AD - Department of Molecular Biology, University of Salzburg, Salzburg, Austria. FAU - Redegeld, Frank A AU - Redegeld FA AD - Division of Pharmacology, Department of Pharmaceutical Sciences, Universiteit Utrecht, Utrecht, The Netherlands. FAU - Brunner, Jens O AU - Brunner JO AD - Chair of Health Care Operations/Health Information Management, UNIKA-T, University of Augsburg, Augsburg, Germany. FAU - Neumann, Avidan U AU - Neumann AU AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. FAU - Traidl-Hoffmann, Claudia AU - Traidl-Hoffmann C AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany; Department of Dermatology, University Clinic Augsburg, Augsburg, Germany; Christine Kuhne - Center for Allergy Research and Education, Davos, Switzerland. FAU - Gilles, Stefanie AU - Gilles S AD - Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Augsburg, Germany. Electronic address: stefanie.gilles@tum.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200406 PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Allergens) RN - 0 (Antigens, Plant) RN - 0 (Biomarkers) RN - 0 (CXCL8 protein, human) RN - 0 (IL33 protein, human) RN - 0 (Immunoglobulin A) RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-33) RN - 0 (Interleukin-8) RN - 126161-14-6 (Bet v 1 allergen, Betula) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Adult MH - Allergens/*immunology MH - Antigens, Plant/*immunology MH - Biomarkers MH - Female MH - Humans MH - Immunoglobulin A/blood/immunology MH - Immunoglobulin E/blood/immunology MH - Immunoglobulin G/blood/immunology MH - Interleukin-33/immunology MH - Interleukin-8/immunology MH - Male MH - Middle Aged MH - Nasal Mucosa/immunology MH - Pollen/*immunology MH - Rhinitis, Allergic, Seasonal/blood/*immunology MH - Seasons MH - Young Adult OTO - NOTNLM OT - Allergic rhinitis OT - biomarkers OT - chemokines OT - cytokines OT - immunoglobulins OT - nasal symptoms OT - pollen EDAT- 2020/04/10 06:00 MHDA- 2021/03/11 06:00 CRDT- 2020/04/10 06:00 PHST- 2019/06/24 00:00 [received] PHST- 2020/01/31 00:00 [revised] PHST- 2020/02/24 00:00 [accepted] PHST- 2020/04/10 06:00 [pubmed] PHST- 2021/03/11 06:00 [medline] PHST- 2020/04/10 06:00 [entrez] AID - S0091-6749(20)30419-X [pii] AID - 10.1016/j.jaci.2020.02.037 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2020 Sep;146(3):583-594.e6. doi: 10.1016/j.jaci.2020.02.037. Epub 2020 Apr 6.