The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Association between specific IgE to staphylococcal enterotoxin B and the eosinophilic phenotype of asthma

  • Soyoon Sim (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Youngwoo Choi (Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science, Pusan National University) ;
  • Eun-Mi Yang (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Hae-Sim Park (Department of Allergy and Clinical Immunology, Ajou University School of Medicine)
  • Received : 2024.01.05
  • Accepted : 2024.04.02
  • Published : 2024.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background/Aims: Sensitization to staphylococcal superantigens (SAgs) could contribute to asthma severity. However, its relevance with eosinophilic phenotype has not yet been clarified. This study aimed to investigate associations between serum specific IgE levels to SAg and eosinophilic airway inflammation in adult asthmatics. Methods: The serum specific IgE levels to 3 SAgs, including staphylococcal enterotoxin A (SEA) and B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured by ImmunoCAP in 230 adult asthmatic patients and 50 healthy controls (HCs). Clinical characteristics and laboratory parameters, including serum total/free IgE, and 2 eosinophil-activation markers, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were analyzed according to blood eosinophil counts (BEC; 150 cells/µL) and serum specific IgE levels to 3 SAgs (0.35 kU/L). Results: Asthmatic patients showed higher serum specific IgE levels to 3 SAgs than HCs (p < 0.05 for all). The serum total/free IgE levels were significantly higher in asthmatics with positive IgE responses to 3 SAgs than those without (p < 0.05 for all). There were no significant differences in clinical parameters including age, asthma severity, comorbidities, or smoking according to IgE responses to 3 SAgs. Patients with positive IgE responses to SEB (not to SEA/TSST-1) had higher serum specific IgE levels to house dust mites and ECP/EDN as well as higher BEC with positive correlations between serum SEB-specific IgE levels and BEC/ECP/EDN (p < 0.05 for all). Conclusions: These findings suggest that serum SEB-specific IgE levels could contribute to eosinophil activation as well as IgE production in adult asthma.

Keywords

Acknowledgement

This research was supported by the Korean Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI) grant funded by the Ministry of Health and Welfare, Republic of Korea (HR16C0001).

References

  1. Sim S, Choi Y, Park HS. Immunologic basis of type 2 biologics for severe asthma. Immune Netw 2022;22:e45.
  2. Nurmagambetov T, Kuwahara R, Garbe P. The economic burden of asthma in the United States, 2008-2013. Ann Am Thorac Soc 2018;15:348-356.
  3. Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 2019;56:219-233.
  4. Choi Y, Sim S, Park HS. Distinct functions of eosinophils in severe asthma with type 2 phenotype: clinical implications. Korean J Intern Med 2020;35:823-833.
  5. McBrien CN, Menzies-Gow A. The biology of eosinophils and their role in asthma. Front Med (Lausanne) 2017;4:93.
  6. Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998;339:520-532.
  7. Liu JN, Shin YS, Yoo HS, et al. The prevalence of serum specific IgE to superantigens in asthma and allergic rhinitis patients. Allergy Asthma Immunol Res 2014;6:263-266.
  8. Xu SX, McCormick JK. Staphylococcal superantigens in colonization and disease. Front Cell Infect Microbiol 2012;2:52.
  9. Du K, Zhao Y, Zhang X, et al. Staphylococcus aureus lysate induces an IgE response via memory B cells in nasal polyps. J Allergy Clin Immunol 2024;153:718-731.e11.
  10. Ong PY, Patel M, Ferdman RM, Dunaway T, Church JA. Association of staphylococcal superantigen-specific immunoglobulin e with mild and moderate atopic dermatitis. J Pediatr 2008;153:803-806.
  11. Li H, Llera A, Malchiodi EL, Mariuzza RA. The structural basis of T cell activation by superantigens. Annu Rev Immunol 1999;17:435-466.
  12. Zhang N, Holtappels G, Gevaert P, et al. Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy 2011;66:141-148.
  13. Flora M, Perrotta F, Nicolai A, et al. Staphylococcus Aureus in chronic airway diseases: an overview. Respir Med 2019;155:66-71.
  14. Kowalski ML, Cieslak M, Perez-Novo CA, Makowska JS, Bachert C. Clinical and immunological determinants of severe/ refractory asthma (SRA): association with Staphylococcal superantigen-specific IgE antibodies. Allergy 2011;66:32-38.
  15. Matsumoto H, Kanemitsu Y, Nagasaki T, et al. Staphylococcus aureus enterotoxin sensitization involvement and its association with the CysLTR1 variant in different asthma phenotypes. Ann Allergy Asthma Immunol 2017;118:197-203.
  16. Song WJ, Sintobin I, Sohn KH, et al. Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly. Clin Exp Allergy 2016;46:411-421.
  17. Chung KF. Staphylococcus aureus enterotoxin-specific IgE sensitization in severe eosinophilic asthma phenotype. Allergy Asthma Immunol Res 2023;15:119-121.
  18. Global Initiative for Asthma. 2023 GINA report, global strategy for asthma management and prevention [Internet]. Fontana (WI): Global Initiative for Asthma, c2023 [cited 2023 Dec 27]. Available from: https://ginasthma.org/2023-gina-mainreport/.
  19. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J 2020;55:1900588.
  20. Woo SD, Yang EM, Jang J, et al. Serum-free immunoglobulin E: a useful biomarker of atopy and type 2 asthma in adults with asthma. Ann Allergy Asthma Immunol 2021;127:109-115.e1.
  21. Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE 'above atopy'. J Intern Med 2012;272:133-143.
  22. Pinheiro-Torres AS, Ferreira-Duarte AP, Takeshita WM, et al. Airways exposure of bacterial superantigen SEB enhances bone marrow eosinophil population and facilitates its egress to blood and lung tissue. Life Sci 2021;264:118685.
  23. Hellings PW, Hens G, Meyts I, et al. Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to Staphylococcus aureus enterotoxin B. Clin Exp Allergy 2006;36:1063-1071.
  24. Abdurrahman G, Schmiedeke F, Bachert C, Broker BM, Holtfreter S. Allergy-a new role for T cell superantigens of Staphylococcus aureus? Toxins (Basel) 2020;12:176.
  25. Huvenne W, Callebaut I, Plantinga M, et al. Staphylococcus aureus enterotoxin B facilitates allergic sensitization in experimental asthma. Clin Exp Allergy 2010;40:1079-1090.
  26. Schleich F, Moermans C, Gerday S, et al. Patients with asthma only sensitized to Staphylococcus aureus enterotoxins have more exacerbations, airflow limitation, and higher levels of sputum IL-5 and IgE. J Allergy Clin Immunol Pract 2023;11:3055-3061.e4.
  27. Bachert C, van Steen K, Zhang N, et al. Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma. J Allergy Clin Immunol 2012;130:376-381.e8.
  28. Matucci A, Vultaggio A, Maggi E, Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res 2018;19:113.
  29. Lee Y, Lee JH, Yang EM, et al. Serum levels of eosinophil-derived neurotoxin: a biomarker for asthma severity in adult asthmatics. Allergy Asthma Immunol Res 2019;11:394-405.
  30. Koh GC, Shek LP, Goh DY, Van Bever H, Koh DS. Eosinophil cationic protein: is it useful in asthma? A systematic review. Respir Med 2007;101:696-705.
  31. Price D, Wilson AM, Chisholm A, et al. Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice. J Asthma Allergy 2016;9:1-12.
  32. Zeiger RS, Schatz M, Dalal AA, et al. Blood eosinophil count and outcomes in severe uncontrolled asthma: a prospective study. J Allergy Clin Immunol Pract 2017;5:144-153.e8.
  33. Solomon Y, Malkamu B, Berhan A, et al. Peripheral blood eosinophilia in adult asthmatic patients and its association with the severity of asthma. BMC Pulm Med 2023;23:96.
  34. Kimura H, Konno S, Makita H, et al. Prospective predictors of exacerbation status in severe asthma over a 3-year follow-up. Clin Exp Allergy 2018;48:1137-1146.
  35. Choi Y, Kim YM, Lee HR, et al. Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma. Allergy 2020;75:95-103.
  36. Choi Y, Le Pham D, Lee DH, Lee SH, Kim SH, Park HS. Biological function of eosinophil extracellular traps in patients with severe eosinophilic asthma. Exp Mol Med 2018;50:1-8.
  37. Gevaert E, Zhang N, Krysko O, et al. Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation. J Allergy Clin Immunol 2017;139:1849-1860.e6.
  38. Kim SH, Yang SY, You J, et al. Association of specific immunoglobulin E to staphylococcal enterotoxin with airway hyper-responsiveness in asthma patients. Tuberc Respir Dis (Seoul) 2016;79:295-301.
  39. Barranco P, Palao P, Ruiz I, et al. Relationship between IgE-mediated sensitization to Staphylococcus aureus enterotoxin B, asthma severity, and atopy. J Investig Allergol Clin Immunol 2021;31:170-173.
  40. Tanaka A, Suzuki S, Ohta S, et al. Association between specific IgE to Staphylococcus aureus enterotoxins A and B and asthma control. Ann Allergy Asthma Immunol 2015;115:191-197.e2.
  41. Elabras J Filho, Mello FC, Lupi O, Bica BE, Papi JA, Franca AT. Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma. J Bras Pneumol 2016;42:356-361.