Total and specific immunoglobulin E in induced sputum in allergic and non-allergic asthma

Astrid Crespo-Lessmann, Elena Curto, Eder Mateus, Lorena Soto, Alba García-Moral, Montserrat Torrejón, Alicia Belda, Jordi Giner, David Ramos-Barbón, Vicente Plaza, Astrid Crespo-Lessmann, Elena Curto, Eder Mateus, Lorena Soto, Alba García-Moral, Montserrat Torrejón, Alicia Belda, Jordi Giner, David Ramos-Barbón, Vicente Plaza

Abstract

Background: Most patients with nonallergic asthma have normal serum immunoglobulin E (IgE) levels. Recent reports suggest that total and aeroallergen-specific IgE levels in induced sputum may be higher in nonallergic asthmatics than in healthy controls. Our objective is to compare total and dust-mite specific (Der p 1) IgE levels in induced sputum in allergic and nonallergic asthmatics and healthy controls.

Methods: Total and Der p 1-specific IgE were measured in induced sputum (ImmunoCAP immunoassay) from 56 age- and sex-matched asthmatics (21 allergic, 35 nonallergic) and 9 healthy controls. Allergic asthma was defined as asthma with a positive prick test and/or clinically-significant Der p 1-specific serum IgE levels.

Results: Patients with allergic asthma presented significantly higher total and Der p 1-specific serum IgE levels. There were no significant between-group differences in total sputum IgE. However, Der p 1-specific sputum IgE levels were significantly higher (p = 0.000) in the allergic asthmatics, but without differences between the controls and nonallergic asthmatics. Serum and sputum IgE levels were significantly correlated, both for total IgE (rho = 0.498; p = 0.000) and Der p 1-specific IgE (rho, 0.621; p = 0001).

Conclusions: Total IgE levels measured in serum and induced sputum are significantly correlated. No significant differences were found between the differents groups in total sputum IgE. Nevertheless, the levels of Der p 1-specific sputum IgE levels were significantly higher in the allergic asthmatics, but without differences between the controls and nonallergic asthmatics. Probably due to the lack of sensitivity of the test used, but with the growing evidence for local allergic reactions better methods are need to explore its presence. The Clinical Trials Identifier for this project is NCT03640936.

Conflict of interest statement

AC. in the last three years received honoraria for speaking at sponsored meetings from AstraZeneca, Chiesi, Esteve Laboratories, Faes Farma, Ferrer, GlaxoSmithKline, Novartis, Teva, Zambon. Received help assistance to meeting travel from Bial, Novartis. Act as a consultant for AstraZeneca, Boehringer, GlaxoSmithKline, Novartis. And received funding/grant support for research projects from a variety of Government agencies and not-for-profit foundations, as well as AstraZeneca. EC has received funding to travel to and attend training activities from ALK, Menarini, Teva, AstraZeneca, Chiesi, Boehringer, and Novartis. LS, EM and declare no conflict of interests. JG has received funding to travel and attend to training activities from Menarini, Teva, AstraZeneca, Chiesi, GSK, Mundipharma, Boehringer. In the last three years, VP has received honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, and Novartis. VP has also received financial support to travel to meetings organized by Chiesi and Novartis. VP is a consultant for ALK, AstraZeneca, Boehringer, MundiPharma, and Sanofi. VP has also received funding/grant support for research projects from a variety of governmental agencies and not-for-profit foundations, as well as from AstraZeneca, Chiesi and Menarini.

Figures

Fig 1. Total IgE in sputum in…
Fig 1. Total IgE in sputum in patients with allergic asthma, non-allergic asthma, and healthy controls.
Fig 2. Der p 1-specific IgE levels…
Fig 2. Der p 1-specific IgE levels in sputum in patients with allergic asthma, non-allergic asthma and healthy controls.

References

    1. Peters SP. Asthma Phenotypes: Nonallergic (Intrinsic) Asthma. J Allergy Clin Immunol Pract 2014;2:650–652. 10.1016/j.jaip.2014.09.006
    1. Froidure A, Mouthuy J, Durham SR, Chanez P, Sibille Y, Pilette C. Asthma phenotypes and IgE responses. Eur Respir J 2016;47:304–319. 10.1183/13993003.01824-2014
    1. Beeh KM, Ksoll M, Buhl R. Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals. Eur Respir J 2000;16:609 10.1034/j.1399-3003.2000.16d07.x
    1. Barnes PJ. Intrinsic asthma: not so different from allergic asthma but driven by superantigens? Clin Exp Allergy 2009;39:1145–1151. 10.1111/j.1365-2222.2009.03298.x
    1. Borriello EM, Vatrella A. Does non-allergic asthma still exist? Shortness of breath 2013;2:55–60.
    1. Vennera MDC, Picado C. Novel diagnostic approaches and biological therapeutics for intrinsic asthma. Int J Gen Med 2014;7:365–371. 10.2147/IJGM.S45259
    1. Mouthuy J, Detry B, Sohy C, Pirson F, Pilette C. Presence in sputum of functional dust mite-specific IgE antibodies in intrinsic asthma. Am J Respir Crit Care Med 2011;184:206–214. 10.1164/rccm.201009-1434OC
    1. de Llano LP, Vennera M del C, Álvarez FJ, Medina JF, Borderías L, Pellicer C, et al. Effects of Omalizumab in Non-Atopic Asthma: Results from a Spanish Multicenter Registry. J Asthma 2013;50:296–301. 10.3109/02770903.2012.757780
    1. Lommatzsch M, Korn S, Buhl R, Virchow JC. Against all odds: Anti-IgE for intrinsic asthma? Thorax 2014;69:94–96. 10.1136/thoraxjnl-2013-203738
    1. Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE ‘above atopy’. J Intern Med 2012;272:133–143. 10.1111/j.1365-2796.2012.02559.x
    1. Lommatzsch M, Stoll P. Novel strategies for the treatment of asthma. Allergo J Int 2016;25:11–17. 10.1007/s40629-016-0093-5
    1. Rondón C, Bogas G, Barrionuevo E, Blanca M, Torres MJ, Campo P. Nonallergic rhinitis and lower airway disease. Allergy 2017;72:24–34. 10.1111/all.12988
    1. Rondón C, Campo P, Zambonino MA, Blanca-Lopez N, Torres MJ, Melendez L, et al. Follow-up study in local allergic rhinitis shows a consistent entity not evolving to systemic allergic rhinitis. J Allergy Clin Immunol 2014;133:1026–1031. 10.1016/j.jaci.2013.10.034
    1. Rondón C, Campo P, Galindo L, Blanca-Lõpez N, Cassinello MS, Rodriguez-Bada JL, et al. Prevalence and clinical relevance of local allergic rhinitis. Allergy Eur J Allergy Clin Immunol 2012;67:1282–1288.
    1. De Schryver E, Devuyst L, Derycke L, Dullaers M, Van Zele T, Bachert C, et al. Local immunoglobulin E in the nasal mucosa: Clinical implications. Allergy, Asthma Immunol Res 2015;7:321–331.
    1. Ying S, Humbert M, Meng Q, Pfister R, Menz G, Gould HJ, et al. Local expression of epsilon germline gene transcripts and RNA for the epsilon heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma. J Allergy Clin Immunol 2001;107:686–692. 10.1067/mai.2001.114339
    1. GINA Report. Global Strategy for Asthma and Prevention. Available from:
    1. Johansson SG. GO, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. 2004;113:832–836. 10.1016/j.jaci.2003.12.591
    1. Merrett J, Merrett TG. Phadiatop—a novel IgE antibody screening test. Clin Exp Allergy 1987;17:409–416.
    1. Vega JM, Badia X, Badiola C, López-Viña A, Olaguíbel JM, Picado C, et al. Validation of the Spanish Version of the Asthma Control Test (ACT). J Asthma 2007;44:867–872. 10.1080/02770900701752615
    1. American Thoracic Society, European Respiratory Society. ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am J Respir Crit Care Med 2005;171:912–930. 10.1164/rccm.200406-710ST
    1. Roca J, Burgos F, Sunyer J, Saez M, Chinn S, Antó JM, et al. References values for forced spirometry. Group of the European Community Respiratory Health Survey. Eur Respir J 1998;11:1354–1362. 10.1183/09031936.98.11061354
    1. Roca J, Sanchis J, Agusti-Vidal A, Segarra F, Navajas D, Rodriguez-Roisin R, et al. Spirometric reference values from a Mediterranean population. Bull Eur Physiopathol Respir 1986;22:217–224.
    1. Crespo-Lessmann AC, Giner J, Torrego A, Mateus E, Torrejón M, Belda A, et al. Usefulness of the exhaled breath temperature plateau in asthma patients. Respiration 2015;90:111–117. 10.1159/000431259
    1. Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, et al. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med 1996;154:308–317. 10.1164/ajrccm.154.2.8756799
    1. Belda J, Leigh R, Parameswaran K, O'Byrne PM, Sears MR, Hargreave FE. Induced Sputum Cell Counts in Healthy Adults. Am J Respir Crit Care Med 2000;161:475–478. 10.1164/ajrccm.161.2.9903097
    1. Humbert M, Grant JA, Taborda-Barata L, Durham SR, Pfister R, Menz G, et al. High-affinity IgE receptor (FcepsilonRI)-bearing cells in bronchial biopsies from atopic and nonatopic asthma. Am J Respir Crit Care Med 1996;153:1931–1937. 10.1164/ajrccm.153.6.8665058
    1. 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 2013;8:e58388 10.1371/journal.pone.0058388
    1. Humbert M, Durham SR, Ying S, Kimmitt P, Barkans J, Assoufi B, et al. IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against "intrinsic" asthma being a distinct immunopathologic entity. Am J Respir Crit Care Med 1996;154:1497–1504. 10.1164/ajrccm.154.5.8912771
    1. Takhar P, Corrigan CJ, Smurthwaite L, O’Connor BJ, Durham SR, Lee TH, et al. Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma. J Allergy Clin Immunol 2007;119:213–218. 10.1016/j.jaci.2006.09.045
    1. Araújo L, Palmares C, Beltrão M, Pereira AM, Fonseca J, Moreira A, et al. Validation of total and specific IgE measurements in induced sputum. J Investig Allergol Clin Immunol 2013;23:330–336.
    1. Margarit G, Belda J, Juárez C, Martínez C, Ramos A, Torrejón M, et al. IgE total en el esputo y suero de pacientes con asma. Allergol Immunopathol 2005;33:48–53.
    1. Ahn JY, Choi BS. Clinical Evaluation of Specific Immunoglobulin E in Sputum in Pediatric Patients. Pediatr Allergy Immunol Pulmonol 2018;31:73–77.
    1. Pillai P, Fang C, Chan Y-C, Shamji MH, Harper C, Wu S-Y, et al. Allergen-specific IgE is not detectable in the bronchial mucosa of nonatopic asthmatic patients. J Allergy Clin Immunol 2014;133:1770–2.e11. 10.1016/j.jaci.2014.03.027
    1. Dakhama A, Park J-W, Taube C, Chayama K, Balhorn A, Joetham A, et al. The Role of Virus-specific Immunoglobulin E in Airway Hyperresponsiveness. Am J Respir Crit Care Med 2004;170:952–959. 10.1164/rccm.200311-1610OC
    1. Valenta R, Seiberler S, Natter S, Mahler V, Mossabeb R, Ring J, et al. Autoallergy: A pathogenetic factor in atopic dermatitis? J Allergy Clin Immunol 2000;105:432–437. 10.1067/mai.2000.104783

Source: PubMed

3
订阅