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

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.

Human exposure to airborne pollen and relationships with symptoms and immune responses: Indoors versus outdoors, circadian patterns and meteorological effects in alpine and urban environments.

Pollen exposure is a major cause of respiratory allergies worldwide. However, it is unclear how everyday exposure is related to symptoms and how allergic patients may be affected spatially and temporally. Hence, we investigated the relationship of pollen, symptoms and immune responses under a controlled regime of 'high-low-moderate' pollen exposure in urban versus alpine environment. The research was conducted in 2016 in two locations in Germany: urban Augsburg (494 m) and Schneefernerhaus (UFS) on Zugspitze mountain (2656 m). Monitoring of airborne pollen took place using Hirst-type volumetric traps. On UFS, both indoor and outdoor samples were taken. Grass pollen allergic human volunteers were monitored daily during the peak of the grass pollen season, in Augsburg, on UFS, then again in Augsburg. Nasal biosamples were obtained throughout the study to investigate immune responses. All symptoms decreased significantly during the stay on UFS and remained low even after the return to Augsburg. The same was observed for nasal total IgE and IgM levels and for nasal type 2 cytokines and chemokines. Augsburg showed higher pollen concentrations than those on UFS. At all sites, pollen were present throughout each day, but were more abundant in Augsburg during morning. On UFS, outdoor pollen levels were up to 6-fold higher than those indoors. Nasal, ocular and pulmonary symptoms correlated with current and previous days' pollen concentrations and relative humidity. Stays in low-exposure environments during the peak pollen season can be an efficient means of reducing allergic symptoms and immune responses. However, in alpine environments, even occasional pollen exposure during short intervals may still trigger symptoms because of the additional environmental stress posed onto allergics. This highlights the need for the consideration of additional environmental factors, apart from symptom diaries and immune responses, so as to efficiently predict high-risk allergy periods.