Patients With Asthma Only Sensitized to Staphylococcus aureus Enterotoxins Have More Exacerbations, Airflow Limitation, and Higher Levels of Sputum IL-5 and IgE.
[en] BACKGROUND: Staphylococcus aureus enterotoxins (SE) may act as superantigens and induce an intense T-cell activation, causing local production of polyclonal IgE and resultant eosinophil activation. OBJECTIVE: To assess whether asthma with sensitization to SE but not to common aeroallergens (AAs) displays different inflammatory characteristics. METHODS: We conducted a prospective study on a series of 110 consecutive patients with asthma recruited from the University Asthma Clinic of Liège. We compared clinical, functional, and inflammatory characteristics of this general population of patients with asthma categorized into 4 groups according to sensitization to AAs and/or SE. We also compared sputum supernatant cytokines in patients sensitized to SE or not. RESULTS: Patients with asthma sensitized only to AAs represented 30%, while 29% were sensitized to both AAs and SE. One-fifth of the population had no specific IgE. Sensitization to SE but not to AA (21%) was associated with later onset of disease, higher rate of exacerbations, nasal polyps, and more severe airway obstruction. As for airway type 2 biomarkers, patients presenting with specific IgE against SE displayed higher fractional exhaled nitric oxide, sputum IgE, and sputum IL-5 levels but not IL-4. We confirm that the presence of specific IgE against SE is associated with elevated serum IgE to levels well above those observed in patients sensitized only to AAs. CONCLUSIONS: Our study suggests that asthma specialists should measure specific IgE against SE during the phenotyping process because it may allow the identification of a subgroup of patients with more asthma exacerbations, more nasal polyposis and chronic sinusitis, lower lung function, and more intense type 2 inflammation.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Schleich, FLorence ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Moermans, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
ZIANT, Stéphanie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Louis, Gilles ; Université de Liège - ULiège > Santé publique : de la Biostatistique à la Promotion de la Santé
Bougard, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
PAULUS, Virginie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
GUISSARD, Françoise ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Henket, Monique ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Bachert, Claus; ENT-Clinic, University Hospital of Münster, Münster, Germany, Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden, Upper Airway Research Laboratory, Ghent University, Ghent, Belgium.
Louis, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Language :
English
Title :
Patients With Asthma Only Sensitized to Staphylococcus aureus Enterotoxins Have More Exacerbations, Airflow Limitation, and Higher Levels of Sputum IL-5 and IgE.
Publication date :
October 2023
Journal title :
Journal of Allergy and Clinical Immunology: In Practice
Huang, Y.J., Boushey, H.A., The microbiome in asthma. J Allergy Clin Immunol 135 (2015), 25–30.
Schleich, F.N., Chevremont, A., Paulus, V., Henket, M., Manise, M., Seidel, L., et al. Importance of concomitant local and systemic eosinophilia in uncontrolled asthma. Eur Respir J 44 (2014), 97–108.
Brusselle, G.G., Maes, T., Bracke, K.R., Eosinophils in the spotlight: eosinophilic airway inflammation in nonallergic asthma. Nat Med 19 (2013), 977–979.
Bachert, C., Zhang, N., Chronic rhinosinusitis and asthma: novel understanding of the role of IgE “above atopy.”. J Intern Med 272 (2012), 133–143.
Schreiber, J., Bröker, B.M., Ehmann, R., Bachert, C., Nonatopic severe asthma might still be atopic: sensitization toward Staphylococcus aureus enterotoxins. J Allergy Clin Immunol 143 (2019), 2279–2280.e2.
Sintobin, I., Siroux, V., Holtappels, G., Pison, C., Nadif, R., Bousquet, J., et al. Sensitisation to staphylococcal enterotoxins and asthma severity: a longitudinal study in the EGEA cohort. Eur Respir J, 54, 2019, 1900198.
Bachert, C., Van Steen, K., Zhang, N., Holtappels, G., Cattaert, T., Maus, B., et al. Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma. J Allergy Clin Immunol 130 (2012), 376–381.
Louis, R., Sele, J., Henket, M., Cataldo, D., Bettiol, J., Seiden, L., et al. Sputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness. Allergy 57 (2002), 907–912.
Kleine-Tebbe, J., Jakob, T., Molecular allergy diagnostics using IgE singleplex determinations: methodological and practical considerations for use in clinical routine: part 18 of the Series Molecular Allergology. Allergo J Int 24 (2015), 185–197.
van Hage, M., Hamsten, C., Valenta, R., ImmunoCAP assays: pros and cons in allergology. J Allergy Clin Immunol 140 (2017), 974–977.
Juniper, E.F., Guyatt, G.H., Epstein, R.S., Ferrie, P.J., Jaeschke, R., Hiller, T.K., Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials 1. Thorax 47 (1992), 76–83.
Juniper, E.F., O'Byrne, P.M., Guyatt, G.H., Ferrie, P.J., King, D.R., Development and validation of a questionnaire to measure asthma control. Eur Respir J 14 (1999), 902–907.
Nathan, R.A., Sorkness, C.A., Kosinski, M., Schatz, M., Li, J.T., Marcus, P., et al. Development of the Asthma Control Test: a survey for assessing asthma control. J Allergy Clin Immunol 113 (2004), 59–65.
Delvaux, M., Henket, M., Lau, L., Kange, P., Bartsch, P., Djukanovic, R., et al. Nebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma. Thorax 59 (2004), 111–115.
Gerday, S., Schleich, F., Henket, M., Guissard, F., Paulus, V., Louis, R., Asthmatics with concordant eosinophilic disease classified according to their serum IgE status. Respir Med Res, 79, 2021, 100797.
Garcia, G., Magnan, A., Chiron, R., Contin-Bordes, C., Berger, P., Taillé, C., et al. A proof-of-concept, randomized, controlled trial of omalizumab in patients with severe, difficult-to-control, nonatopic asthma. Chest 144 (2013), 411–419.
Moermans, C., Brion, C., Bock, G., Graff, S., Gerday, S., Nekoee, H., et al. Sputum type 2 markers could predict remission in severe asthma treated with anti-IL-5. Chest 163 (2023), 1368–1379.
Caruso, C., Colantuono, S., Ciasca, G., Basile, U., Di Santo, R., Bagnasco, D., et al. Different aspects of severe asthma in real life: role of Staphylococcus aureus enterotoxins and correlation to comorbidities and disease severity. Allergy 78 (2023), 131–140.
Wang, X., Zhang, N., Bo, M., Holtappels, G., Zheng, M., Lou, H., et al. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol 138 (2016), 1344–1353.
Guida, G., Rolla, G., Badiu, I., Marsico, P., Pizzimenti, S., Bommarito, L., et al. Determinants of exhaled nitric oxide in chronic rhinosinusitis. Chest 137 (2010), 658–664.
Naclerio, R., Baroody, F., Bachert, C., Bleier, B., Borish, L., Brittain, E., et al. Clinical research needs for the management of chronic rhinosinusitis with nasal polyps in the new era of biologics: a National Institute of Allergy and Infectious Diseases workshop. J allergy Clin Immunol Pract 8 (2020), 1532–15349.e1.
Schubert, M.S., A superantigen hypothesis for the pathogenesis of chronic hypertrophic rhinosinusitis, allergic fungal sinusitis, and related disorders. Ann Allergy Asthma Immunol 87 (2001), 181–188.
Gevaert, E., Zhang, N., Krysko, O., Lan, F., Holtappels, G., De Ruyck, N., 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 139 (2017), 1849–1860.e6.
Persson, E.K., Verstraete, K., Heyndrickx, I., Gevaert, E., Aegerter, H., Percier, J.-M., et al. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. Science, 364, 2019, eaaw4295.
Manise, M., Holtappels, G., Van Crombruggen, K., Schleich, F., Bachert, C., Louis, R., Sputum IgE and cytokines in asthma: relationship with sputum cellular profile. PLoS One, 8, 2013, e58388.
Bachert, C., Wagenmann, M., Hauser, U., Rudack, C., IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol 99 (1997), 837–842.