Exploring the association between interleukin-27 and Dermatophagoides-specific IgE responses in children with allergic rhinitis and asthma
Main Article Content
Keywords
Allergy, interleukin, Dermatophagoides pteronyssinus
Abstract
Purpose: House dust mite (HDM) allergy is a common cause of allergic rhinitis (AR) and allergic asthma (AA). Interleukin-27 (IL-27) is known to suppress Th2-mediated inflamma-tion, a key driver of these diseases. This study aimed to assess regional sensitization to Dermatophagoides subspecies and to investigate the association between HDM-specific IgE responses and serum IL-27 levels.
Methods: Fifty-eight children with HDM allergy were evaluated, of whom 53 were sensitized to D. Pteronyssinus. Serum Der p 1/Der p 2 specific IgE (sIgE) (FEIA) and IL-27, IL-5, and IL-13 levels (ELISA) were measured. Twenty-five healthy children served as controls.
Results: Among patients (43% AR, 57% AA), Der p 1 and Der p 2 sensitization rates were 49% and 55%, respectively. Both Der p 1/Der p 2 sIgE levels were significantly elevated compared to controls (p < 0.001). Although IL-27 levels were lower in patients, the difference was not statistically significant (p = 0.98). However, IL-27 showed positive correlations with IL-5, IL-13, and Der p 1 sIgE (all p < 0.05). IL-27 levels were unexpectedly higher in Der p 1–sensitized patients (p = 0.006), particularly in AR (p = 0.02; r = 0.43), but not in AA.
Conclusions: This is the first clinical study to investigate the relationship between IL-27 and HDM-sIgE in children and to demonstrate a phenotype-specific interaction. IL-27 may act as a context-dependent immunomodulator rather than a simple Th2 suppressor. The positive correlation between IL-27 and Der p 1 sIgE in AR patients may indicate a compensatory feedback mechanism triggered by allergen-specific inflammation.
References
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20. Kidon MI, Chiang WC, Liew WK, et al. Mite component-spesific IgE reporoire and phenotypes of allergic disease in childhood: the tropical perspective. Pediatr Allergy Immunol. 2011;22(2):202-10. https://doi. org/10.1111/j.1399-3038.2010.01094.x
21. Resch Y, Michel S, Lupinek C, Valenta R, Vrtala S. Different IgE recognition of mite allergen components in asthmatic and nonasthmatic children. J Allergy Clin Immunol. 2015;136:1083-91. https://doi.org/10.1016/j.jaci.2015.03.024
22. Vidal C, Loio S, Juangorena M, Gonzalez-Quintela A. Association between asthma and sensitization to allergens of Dermatophagoides pteronyssinus. J Investig Allergol Clin Immunol. 2016;26(5):304-309. https://doi.org/10.18176/ jiaci.0048
23. Til-Perez G, Carnevale C, Sarriechegaray PL, Arancibia-Tagle D, Chugo-Gordillo S, Tomas-Barberan MD. Sensitization profile in patients with respiratory allergic diseases:differences between conventional and molecular diagnosis (a cross sectional study). Clin Mol Allergy. 2019;2;17:8. https://doi. org/10.1186/s12948-019-0112-4
24. Limao R, Spinola Santos A, Araujo L, et al. Molecular profile of sensitization to Dermatophagoides pteronyssinus dust mite in Portugal. J Investig Allergol Clin Immunol. 2021;32(1):33-39. https://doi.org/10.18176/jiaci.0533
25. Hasegawa A, Utsumi D, Lund K, Okano M, Ohashi-Doi K, Okubo K. Correlation between sensitization to house dust mite major allergens, age, and symptoms in Japanese house dust mite allergic subjects. Int Immunopharmacol. 2022; 107:108640. https://doi.org/10.1016/j.intimp.2022.108640
26. Yazici S, Gunes S, Kurtulus-Cokboz M, et al. Allergen variability and house dust mite sensitivity in pre-school children with allergic complaints. Turk J Pediatr. 2018;60(1):41-49. https://doi.org/10.24953/turkjped.2018.01.006
27. Su X, Pan J, Bai F, et al. (2016) IL-27 attenuates airway inflammation in a mouse asthma model via the STAT1 and GADD45γ/p38 MAPK pathways. J Transl Med. 2016;14(1):283. https://doi.org/10.1186/s12967-016-1039-x
28. Suzuki M, Yokota M, Ozaki S, Matsumoto T. Intranasal administration of IL-27 ameliorates nasal allergic responses and symptoms. Int Arch Allergy Immunol. 2019;178(2):101-105. https://doi.org/10.1159/000493398
29. Lu D, Lu J, Ji X, et al. IL27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma. Int J Mol Med. 2020;46(2):641-652. https://doi.org/10.3892/ijmm.2020.4622
30. Ouyang H, Cheng J, Du J, Gan H, Zheng L. Interleukin-27 suppresses T Helper-17 inflammation in allergic rhinitis. Iran J Immunol. 2020;17(4):275-282. https://doi.org/10.22034/ iji.2020.84871.1675
31. Fan D, Wang X, Wang M, et al. Allergen-dependent differences in ILC2s frequencies in patients with allergic rhinitis. Allergy Asthma Immunol Res. 2016;30; 8(3):216-222. https:// doi.org/10.4168/aair.2016.8.3.216
32. Elazab SZ, Hessam WF. Effect of allergen specific immuno-therapy on serum levels of IL-17 and IL-35 in allergic rhinitis patients. Egypt J Immunol. 2017;24(2):101-107.
33. Gan H, Du J, Ouyang H, Cheng J, Mao H. Interleukin-27 inhibits helper T cell type-2 response in allergic rhinitis. Auris Nasus Larynx. 2020;47(1):84-89. https://doi.org/10.1016/j. anl.2019.05.005
34. Qin L, Li Z, Fan Y, et al. Exploration of plasma interleukin-27 levels in asthma patients and the correlation with lung function. Res Med. 2020;175:106208. https://doi.org/10.1016/j. rmed.2020.106208
35. Xie M, Mustovich AT, Jiang Y, et al. IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling. J Allergy Clin Immunol. 2015;135(2):386-94. https://doi. org/10.1016/j.jaci.2014.08.023
36. Liu X, Li S, Jin J, et al. Preventative tracheal administration of interleukin-27 attenuates allergic asthma by improving the lung Th1 microenvironment. J Cellular Physiol. 2019;234(5):6642-6653. https://doi.org/10.1002/jcp.27422
2. Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma allergic rhino-conjunctivitis and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet. 2006;368(9537):733-43. https://doi.org/10.1016/S0140-6736(06) 69283-0
3. WHO/IUIS allergen nomenclature sub-committee. Allergen nomenclature, 2025. Available at: http://www.allergen.org (Accessed: 10 June 2025).
4. Kowal K, Pampuch A, Siergiejko G, et al. Sensitization to major Dermatophagoides pteronyssinus allergens in house dust mite allergic patients from North Eastern Poland developing rhinitis or asthma. Adv Med Sci. 2020;65(2):304-309. https://doi.org/10.1016/j.advms.2020.05.003
5. Bronnert M, Mancini J, Birnbaum J, et al. Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite allergy. Clin Exp Allergy. 2012;42(9):1406-1415. https://doi.org/10.1111/j.1365-2222.2012.04035.x
6. Zou X, Hu H, Huang Z, et al. Serum levels of specific immunoglobulin E to Dermatophagoides pteronyssinus allergen components in patients with allergic rhinitis or/and asthma. Allergy Asthma Proc. 2021;42(1):e40-e46. https://doi. org/10.2500/aap.2021.42.200105.
7. De Oliveira JR, da Silva PR, Rogerio AP. AT-RvD1 modulates the activation of bronchial epithelial cells induced by lipopolysaccharide and Dermatophagoides pteronyssinus. European J Pharmacol. 2017;805:46-50. https://doi. org/10.1016/j.ejphar.2017.03.029
8. Wenzel SE. Asthma pheotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716-25. https:// doi.org/10.1038/nm.2678.
9. Kato A. Group 2 innate lymphoid cells in airway diseases. Chest. 2019;156(1):141-149. https://doi.org/10.1016/j.chest. 2019.04.101
10. Doherty TA, Scott D, Walford HH, et al. Allergen challenge in allergic rhinitis rapidly induces increased peripheral blood type 2 innate lymphoid cells that express CD84. J Allergy Clin Immunol. 2014;133(4):1203-5. https://doi.org/10.1016/j. jaci.2013.12.1086
11. Jafarzadeh A, Nemati M, Jafarzadeh S, Chauhan P, Saha B. The immunomodulatory potentials of interleukin-27 in airway allergies. Scan J Immunol. 2021;93(2):e12959. https:// doi.org/10.1111/sji.12959
12. Stumhofer JS, Laurence A, Wilson EH, et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol. 2006;7(9):937-45. https:// doi.org/10.1038/ni1376
13. Moro K, Kabata H, Tanabe M, et al. Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses. Nat Immunol. 2016;17(1): 76-86. https://doi.org/10.1038/ni.3309
14. Mchedlidze T, Kindermann M, Neves AT, Voehringer D, Neurath MF, Wirtz S. IL-27 suppresses type 2 immune responses in vivo via direct effects on group 2 innate lymphoid cells. Mucosal Immunol. 2016;9(6):1384-1394. https:// doi.org/10.1038/mi.2016.20
15. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. BMJ. 2007;20;335(7624):806-8. https://doi.org/10.1136/ bmj.39335.541782.AD
16. Can C, Altinel N, Hatipoglu S. Aeroallergen sensitization patterns of children aged 5 years and younger with asthma and/ or allergic rhinitis in Istanbul. Arch Pediatr. 2021;28(1):7-11. https://doi.org/10.1016/j.arcped.2020.10.014
17. Christianson CA, Goplen NP, Zafar I, et al. Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33. J Allergy Clin Immunol. 2015;136(1):59-68.e14. https://doi.org/10.1016/j. jaci.2014.11.037
18. Luo X, Zeng Q, Li Y, Tang Y, Liu W, Luo R. The inhibition of group II innate lymphoid cell response by IL-27 in allergic rhinitis. J Immunol Res Dec. 2020;16;2020:6661524. https://doi. org/10.1155/2020/6661524
19. Batard T, Baron-Bodo V, Martelet A, et al. Patterns of IgE sensitization in house dust mite allergic patients: implications for allergen immunotherapy. Allergy. 2016;71:220-9. https://doi.org/10.1111/all.12796
20. Kidon MI, Chiang WC, Liew WK, et al. Mite component-spesific IgE reporoire and phenotypes of allergic disease in childhood: the tropical perspective. Pediatr Allergy Immunol. 2011;22(2):202-10. https://doi. org/10.1111/j.1399-3038.2010.01094.x
21. Resch Y, Michel S, Lupinek C, Valenta R, Vrtala S. Different IgE recognition of mite allergen components in asthmatic and nonasthmatic children. J Allergy Clin Immunol. 2015;136:1083-91. https://doi.org/10.1016/j.jaci.2015.03.024
22. Vidal C, Loio S, Juangorena M, Gonzalez-Quintela A. Association between asthma and sensitization to allergens of Dermatophagoides pteronyssinus. J Investig Allergol Clin Immunol. 2016;26(5):304-309. https://doi.org/10.18176/ jiaci.0048
23. Til-Perez G, Carnevale C, Sarriechegaray PL, Arancibia-Tagle D, Chugo-Gordillo S, Tomas-Barberan MD. Sensitization profile in patients with respiratory allergic diseases:differences between conventional and molecular diagnosis (a cross sectional study). Clin Mol Allergy. 2019;2;17:8. https://doi. org/10.1186/s12948-019-0112-4
24. Limao R, Spinola Santos A, Araujo L, et al. Molecular profile of sensitization to Dermatophagoides pteronyssinus dust mite in Portugal. J Investig Allergol Clin Immunol. 2021;32(1):33-39. https://doi.org/10.18176/jiaci.0533
25. Hasegawa A, Utsumi D, Lund K, Okano M, Ohashi-Doi K, Okubo K. Correlation between sensitization to house dust mite major allergens, age, and symptoms in Japanese house dust mite allergic subjects. Int Immunopharmacol. 2022; 107:108640. https://doi.org/10.1016/j.intimp.2022.108640
26. Yazici S, Gunes S, Kurtulus-Cokboz M, et al. Allergen variability and house dust mite sensitivity in pre-school children with allergic complaints. Turk J Pediatr. 2018;60(1):41-49. https://doi.org/10.24953/turkjped.2018.01.006
27. Su X, Pan J, Bai F, et al. (2016) IL-27 attenuates airway inflammation in a mouse asthma model via the STAT1 and GADD45γ/p38 MAPK pathways. J Transl Med. 2016;14(1):283. https://doi.org/10.1186/s12967-016-1039-x
28. Suzuki M, Yokota M, Ozaki S, Matsumoto T. Intranasal administration of IL-27 ameliorates nasal allergic responses and symptoms. Int Arch Allergy Immunol. 2019;178(2):101-105. https://doi.org/10.1159/000493398
29. Lu D, Lu J, Ji X, et al. IL27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma. Int J Mol Med. 2020;46(2):641-652. https://doi.org/10.3892/ijmm.2020.4622
30. Ouyang H, Cheng J, Du J, Gan H, Zheng L. Interleukin-27 suppresses T Helper-17 inflammation in allergic rhinitis. Iran J Immunol. 2020;17(4):275-282. https://doi.org/10.22034/ iji.2020.84871.1675
31. Fan D, Wang X, Wang M, et al. Allergen-dependent differences in ILC2s frequencies in patients with allergic rhinitis. Allergy Asthma Immunol Res. 2016;30; 8(3):216-222. https:// doi.org/10.4168/aair.2016.8.3.216
32. Elazab SZ, Hessam WF. Effect of allergen specific immuno-therapy on serum levels of IL-17 and IL-35 in allergic rhinitis patients. Egypt J Immunol. 2017;24(2):101-107.
33. Gan H, Du J, Ouyang H, Cheng J, Mao H. Interleukin-27 inhibits helper T cell type-2 response in allergic rhinitis. Auris Nasus Larynx. 2020;47(1):84-89. https://doi.org/10.1016/j. anl.2019.05.005
34. Qin L, Li Z, Fan Y, et al. Exploration of plasma interleukin-27 levels in asthma patients and the correlation with lung function. Res Med. 2020;175:106208. https://doi.org/10.1016/j. rmed.2020.106208
35. Xie M, Mustovich AT, Jiang Y, et al. IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling. J Allergy Clin Immunol. 2015;135(2):386-94. https://doi. org/10.1016/j.jaci.2014.08.023
36. Liu X, Li S, Jin J, et al. Preventative tracheal administration of interleukin-27 attenuates allergic asthma by improving the lung Th1 microenvironment. J Cellular Physiol. 2019;234(5):6642-6653. https://doi.org/10.1002/jcp.27422