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Relationship between IgE Levels Specific for Ragweed Pollen Extract, Amb a 1 and Cross-Reactive Allergen Molecules

Zbîrcea, Lauriana-Eunice, Buzan, Maria-Roxana, Grijincu, Manuela, Babaev, Elijahu, Stolz, Frank, Valenta, Rudolf, Păunescu, Virgil, Panaitescu, Carmen, Chen, Kuan-Wei·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms24044040PMC PMC9962666
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Abstract

Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization.

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Figure 1 Box plot representation of specific IgE levels tested in ImmunoCAP (median = horizontal bars, boxes = interquartile range (IQR), whiskers = minimum and maximum not exceeding IQR; asterisks represent outliers exceeding 3.0 x IQR) against ragweed and other relevant pollen allergens (x-axis) in the study cohort (n = 150). Results are expressed as kUA/L (y-axis).
Figure 1 Box plot representation of specific IgE levels tested in ImmunoCAP (median = horizontal bars, boxes = interquartile range (IQR), whiskers = minimum and maximum not exceeding IQR; asterisks represent outliers exceeding 3.0 x IQR) against ragweed and other relevant pollen allergens (x-axis) in the study cohort (n = 150). Results are expressed as kUA/L (y-axis).CC BY · PubMed Central
Figure 2 The percentage of patients showing different nAmb a 1 sIgE levels corresponding to ragweed extract IgE levels in 150 patients. nAmb a 1 sIgE value (kUA/L) was divided to extract sIgE to obtain the percentage for each patient. Based on the results obtained, patients were divided in 5 groups: nAmb a 1 sIgE made up to 10% of the extract sIgE, nAmb a 1 between 11 and 50%, nAmb a 1 between 51 and 80%, nAmb a 1 between 81 and 100%, and nAmb a 1 higher than extract.
Figure 2 The percentage of patients showing different nAmb a 1 sIgE levels corresponding to ragweed extract IgE levels in 150 patients. nAmb a 1 sIgE value (kUA/L) was divided to extract sIgE to obtain the percentage for each patient. Based on the results obtained, patients were divided in 5 groups: nAmb a 1 sIgE made up to 10% of the extract sIgE, nAmb a 1 between 11 and 50%, nAmb a 1 between 51 and 80%, nAmb a 1 between 81 and 100%, and nAmb a 1 higher than extract.CC BY · PubMed Central
Figure 3 Allergenic activity of ragweed and mugwort profilins. RBL cells were loaded with sera of seven patients and stimulated with different concentrations of rAmb a 8 and rArt v 4; x-axes. β-hexosaminidase releases are expressed as percentages of total mediator contents +/− SD (y-axes). The allergenic activity of nAmb a 1 was evaluated in all patients as a reference.
Figure 3 Allergenic activity of ragweed and mugwort profilins. RBL cells were loaded with sera of seven patients and stimulated with different concentrations of rAmb a 8 and rArt v 4; x-axes. β-hexosaminidase releases are expressed as percentages of total mediator contents +/− SD (y-axes). The allergenic activity of nAmb a 1 was evaluated in all patients as a reference.CC BY · PubMed Central
Figure 4 IgE reactivity to calcium-binding proteins rAmb a 9, rAmb a 10 and rArt v 5 was determined in ELISA assays using sera from ragweed-allergic patients (n = 150). The optical density values (OD 405 nm) displayed on the y-axis correspond to the levels of IgE antibodies. The cut-off value is indicated for Amb a 9 (0.1317), Amb a 10 (0.1453) and Art v 5 (0.100) allergens (horizontal line).
Figure 4 IgE reactivity to calcium-binding proteins rAmb a 9, rAmb a 10 and rArt v 5 was determined in ELISA assays using sera from ragweed-allergic patients (n = 150). The optical density values (OD 405 nm) displayed on the y-axis correspond to the levels of IgE antibodies. The cut-off value is indicated for Amb a 9 (0.1317), Amb a 10 (0.1453) and Art v 5 (0.100) allergens (horizontal line).CC BY · PubMed Central
Figure 5 Association of the IgE response with clinical symptoms: patients show specific IgE levels to ragweed extract, Amb a 1 and Amb a 8 (x-axis) in relation to (a) prevalence of different symptoms and (b) the number of symptoms. Results are expressed as kUA/L (y-axis) (median = horizontal bars, boxes = IQR, whiskers = minimum and maximum not exceeding IQR; asterisks represent outliers exceeding 3.0 x IQR). (c) Prevalence of different symptoms and (d) number of symptoms (x-axis) in relation to reactivity towards any of the pan-allergens Amb a 8, Amb a 9 and Amb a 10 was expressed as percentage of patients (y-axis).
Figure 5 Association of the IgE response with clinical symptoms: patients show specific IgE levels to ragweed extract, Amb a 1 and Amb a 8 (x-axis) in relation to (a) prevalence of different symptoms and (b) the number of symptoms. Results are expressed as kUA/L (y-axis) (median = horizontal bars, boxes = IQR, whiskers = minimum and maximum not exceeding IQR; asterisks represent outliers exceeding 3.0 x IQR). (c) Prevalence of different symptoms and (d) number of symptoms (x-axis) in relation to reactivity towards any of the pan-allergens Amb a 8, Amb a 9 and Amb a 10 was expressed as percentage of patients (y-axis).CC BY · PubMed Central
Figure 6 Diagnosis algorithm and decision tree for identification of ragweed pollen allergy by CRD in areas where ragweed, mugwort, birch and timothy grass pollen are found. Patients with symptoms of allergic rhinitis during the ragweed pollen season and a positive SPT/IgE assay to ragweed pollen extract are further investigated to detect IgE antibodies in serum to Amb a 1, Amb a 4, Amb a 8 and Amb a 9. Additionally, investigation of the IgE antibodies to cross-reactive molecules, homologous to ragweed allergens (i.e., Art v 1, Art v 4, Art v 5, Art v 6, Bet v 2, Bet v 4, Phl p 12 and Phl p 7), are recommended before AIT prescription.
Figure 6 Diagnosis algorithm and decision tree for identification of ragweed pollen allergy by CRD in areas where ragweed, mugwort, birch and timothy grass pollen are found. Patients with symptoms of allergic rhinitis during the ragweed pollen season and a positive SPT/IgE assay to ragweed pollen extract are further investigated to detect IgE antibodies in serum to Amb a 1, Amb a 4, Amb a 8 and Amb a 9. Additionally, investigation of the IgE antibodies to cross-reactive molecules, homologous to ragweed allergens (i.e., Art v 1, Art v 4, Art v 5, Art v 6, Bet v 2, Bet v 4, Phl p 12 and Phl p 7), are recommended before AIT prescription.CC BY · PubMed Central

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Authors
Zbîrcea, L.-E., Buzan, M.-R., Grijincu, M., Babaev, E., Stolz, F., Valenta, R., Păunescu, V., Panaitescu, C., & Chen, K.-W.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-02-17
Volume
24
Issue
4
Pages
4040
ISSN
1422-0067
DOI
10.3390/ijms24044040
PMC
PMC9962666
Cited by
22
References
0
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Authority for Scientific Research and Innovation (ANCSI), under the Operational Program Competitiveness 2014-2020, project INSPIRED (Innovative Strategies for Prevention, Diagnosis and Therapy of Ragweed Pollen Induced Respiratory Diseases). (COP 2014-2020 92/09.09.2016, MySMIS 103663, -)
  • Danube Allergy Research Cluster program funded by the Country of Lower Austria (COP 2014-2020 92/09.09.2016, MySMIS 103663, -)

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