IgE Test in Secretions of Patients with Respiratory Allergy

  • Carmen Rondón
  • Ibon Eguíluz-Gracia
  • Mohamed H. Shamji
  • Janice A. Layhadi
  • María Salas
  • María José Torres
  • Paloma CampoEmail author
Immunologic/Diagnostic Tests in Allergy (P Matricardi, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Immunologic/Diagnostic Tests in Allergy


Purpose of Review

IgE is a key player in multiple inflammatory airway diseases. Ample literature demonstrates its presence in mucosa of patients with allergic rhinitis (AR), local allergic rhinitis (LAR), asthma, or chronic rhinosinusitis with nasal polyposis (CRSwNP).

Recent Findings

Current evidence shows that high-affinity IgE in blood stream of allergic individuals derives mainly from the mucosae. Also, mucosal synthesis of IgE can occur in the absence of systemic atopy, and may be relevant in atopic and non-atopic phenotypes of rhinitis as demonstrated in LAR. Specific IgE (sIgE) detection varies depending on technique used for sample collection and its measurement. sIgE detection is highly specific for diagnosis of LAR. Moreover, measurement of sIgE in secretions could be useful in monitoring response to allergen-specific immunotherapy in both AR and LAR phenotypes.


This review will focus on recent developments in the role of IgE in respiratory diseases, and the clinical implications of its measurement in secretions.


Allergic IgE Local allergic rhinitis Rhinitis Allergen-specific immunotherapy 



The authors’ research is supported by the Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofounded by European Regional Development Fund (ERDF)): ARADyAL RD16/0006/0001, FIS PI12/00900, FIS PI14/00864, and FIS PI17/01410; Andalusian Regional Ministry Health grants PI-0346-2016 and PC-0098-2017; and Institute of Health “Carlos III” through its “Rio Hortega” funding scheme (CM17/00140). Dr. Shamji reports grants from Immune Tolerance Network, NIAID, Regeneron, USA, and grants from Biotech Tools, outside the submitted work.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Dullaers M, Ramadani F, Gould HJ, Gevaert P, Lambrecht BN. The who, where, and when of IgE in allergic airway disease. J Allergy Clin Immunol. 2012;129(3):635–45.PubMedGoogle Scholar
  2. 2.
    De Schryver E, Derycke L, Dullaers M, Van Zele T, Bachert C, Gevaert P. Local immunoglobulin e in the nasal mucosa: clinical implications. Allergy, Asthma Immunol Res. 2015;7(4):321–31.Google Scholar
  3. 3.
    Fokkens WJ, Vinke JG, KleinJan A. Local IgE production in the nasal mucosa: a review. Am J Rhinol. 2000;14(5):299–303.PubMedGoogle Scholar
  4. 4.
    Klein U, Dalla-Favera R. Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol. 2008;8(1):22–3.PubMedGoogle Scholar
  5. 5.
    Kurosaki T, Ise W. Memory B cells. Nat Rev Immunol. 2015;15(3):149–59.PubMedGoogle Scholar
  6. 6.
    He JS, Narayanan S, Subramaniam S, Ho WQ, Lafaille JJ, Curotto de Lafaille MA. Biology of IgE production: IgE cell differentiation and the memory of IgE responses. Curr Top Microbiol Immunol. 2015;388:1–19.PubMedGoogle Scholar
  7. 7.
    Wu LC. The production and regulation of IgE by the immune system. Nat Rev Immunol. 2014;14(4):247–59.PubMedGoogle Scholar
  8. 8.
    Tong P. Molecular mechanisms of IgE class switch recombination. Curr Top Microbiol Immunol. 2015;388:21–37.PubMedGoogle Scholar
  9. 9.
    Xiong H, Wabl M, Curotto de Lafaille MA, Lafaille JJ. Sequential class switching is required for the generation of high affinity IgE antibodies. J Exp Med. 2012;13(209(2)):353–64.Google Scholar
  10. 10.
    He JS, Meyer-Hermann M, Xiangying D, Zuan LY, Jones LA, Ramakrishna L, et al. The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response. J Exp Med. 2013;18(210(12)):2755–71.Google Scholar
  11. 11.
    Coker HA, Gould HJ. Local somatic hypermutation and class switch recombination in the nasal mucosa of allergic rhinitis patients. J Immunol. 2003;171(10):5602–10.PubMedGoogle Scholar
  12. 12.
    KleinJan A, Vinke JG, Severijnen LW, Fokkens WJ. Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients. Eur Respir J. 2000;15(3):491–7.PubMedGoogle Scholar
  13. 13.
    Cameron L, Frenkiel S, Lavigne F, Vercelli D, Hamid Q. S epsilon S mu and S epsilon S gamma switch circles in human nasal mucosa following ex vivo allergen challenge: evidence for direct as well as sequential class switch recombination. J Immunol. 2003;171(7):3816–22.PubMedGoogle Scholar
  14. 14.
    Takhar P, Smurthwaite L, Coker HA, Fear DJ, Banfield GK, Carr VA, et al. Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis. J Immunol. 2005;174(8):5024–32.PubMedGoogle Scholar
  15. 15.
    Gevaert P, Nouri-Aria KT, Wu H, Harper CE, Takhar P, Fear DJ, et al. Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. Allergy. 2013;68(1):55–63.PubMedGoogle Scholar
  16. 16.
    Zhang N, Holtappels G, Gevaert P, Patou J, Dhaliwal B, Gould H, et al. Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy. 2011;66(1):141–8.PubMedGoogle Scholar
  17. 17.
    •• Berings M, Arasi S, De Ruyck N, Perna S, Resch Y, Lupinek C, et al. Reliable mite-specific IgE testing in nasal secretions by means of allergen microarray. J Allergy Clin Immunol. 2017;140(1):301–3 e8. Investigators used a customized microarray containing 15 house dust mite allergen molecules based ImmunoCAP solid-phase allergen chip technology for sIgE detection in nasal secretions of 30 adult patients with AR by house dust mites and 29 non-allergic controls. Samples were obtained with filter disks and sinus packs. Detection of sIgE to at least one of the major allergen molecules (nDer p 1, nDer f 1, rDer p 2, rDer f 2, rDer p23) in nasal secretions predicted with high sensitivity and excellent specificity the allergic status of the patient and the outcome in serum (specificity 100% for both filter disks and sinus packs; sensitivity 90% for filter disks and 87% for sinus packs). PubMedGoogle Scholar
  18. 18.
    Eckl-Dorna J, Pree I, Reisinger J, Marth K, Chen KW, Vrtala S, et al. The majority of allergen-specific IgE in the blood of allergic patients does not originate from blood-derived B cells or plasma cells. Clin Exp Allergy. 2012;42(9):1347–55.PubMedGoogle Scholar
  19. 19.
    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(1):213–8.PubMedGoogle Scholar
  20. 20.
    Rondon C, Romero JJ, Lopez S, Antunez C, Martin-Casanez E, Torres MJ, et al. Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis. J Allergy Clin Immunol. 2007;119(4):899–905.PubMedGoogle Scholar
  21. 21.
    Rondon C, Fernandez J, Lopez S, Campo P, Dona I, Torres MJ, et al. Nasal inflammatory mediators and specific IgE production after nasal challenge with grass pollen in local allergic rhinitis. J Allergy Clin Immunol. 2009;124(5):1005–11 e1.PubMedGoogle Scholar
  22. 22.
    • Campo P, Plaza-Seron MC, Eguiluz-Gracia I, Verge J, Galindo L, Barrionuevo E, et al. Direct intranasal application of the solid phase of ImmunoCAP increases nasal specific IgE detection in local allergic rhinitis. Int Forum Allergy Rhinol. 2018;8(1):15–9 This work evaluated a minimally invasive method of direct detection of nasal sIgE (NsIgE) in patients with LAR to D. pteronyssinus (DP). This was performed by direct application of the solid phase of a commercial DP ImmunoCAP® test 24 h after DP nasal provocation in 50 patients (LAR, n = 14; allergic rhinitis (AR), n = 20; healthy controls n = 16). NsIgE ≥0.1450 was the optimal cut-off point, obtaining in LAR patients 42.86% sensitivity with the highest specificity (100%), and 75% sensitivity and 100% specificity for AR, demonstrating the detection of NsIgE to DP in LAR by using a simple, commercial device with high specificity. PubMedGoogle Scholar
  23. 23.
    Gomez E, Campo P, Rondon C, Barrionuevo E, Blanca-Lopez N, Torres MJ, et al. Role of the basophil activation test in the diagnosis of local allergic rhinitis. J Allergy Clin Immunol. 2013;132(4):975–6 e1–5.PubMedGoogle Scholar
  24. 24.
    Campo P, Villalba M, Barrionuevo E, Rondon C, Salas M, Galindo L, et al. Immunologic responses to the major allergen of Olea europaea in local and systemic allergic rhinitis subjects. Clin Exp Allergy. 2015;45(11):1703–12.PubMedGoogle Scholar
  25. 25.
    Tada T. Distribution of gamma E-forming cells in lymphoid tissues of the human and monkey. J Immunol. 1970;104(2):377–87.PubMedGoogle Scholar
  26. 26.
    Ishizaka K. Presence of gammaE in nasal washings and sputum from asthmatic patients. J Allergy Clin Immunol. 1970;46(4):197–204.Google Scholar
  27. 27.
    Tse KS, Arbesman CE. IgE antibodies in nasal secretions of ragweed-allergic subjects. J Allergy Clin Immunol. 1970;46(6):352–7.Google Scholar
  28. 28.
    Platts-Mills TA. Local production of IgG, IgA and IgE antibodies in grass pollen hay fever. J Immunol. 1979;122(6):2218–25.PubMedGoogle Scholar
  29. 29.
    Sensi LG, Piacentini GL, Nobile E, Ghebregzabher M, Brunori R, Zanolla L, et al. Changes in nasal specific IgE to mites after periods of allergen exposure-avoidance: a comparison with serum levels. Clin Exp Allergy. 1994;24(4):377–82.PubMedGoogle Scholar
  30. 30.
    Smurthwaite L, Wilson DR, Birch DS, Merrett TG, Durham SR, et al. Persistent IgE synthesis in the nasal mucosa of hay fever patients. Eur J Immunol. 2001;31:3422–31.PubMedGoogle Scholar
  31. 31.
    Erazo A, Kutchukhidze N, Leung M, Christ AP, Urban JF Jr, Curotto de Lafaille MA, et al. Unique maturation program of the IgE response in vivo. Immunity. 2007;26(2):191–203.PubMedPubMedCentralGoogle Scholar
  32. 32.
    • Wu YC, James LK, Vander Heiden JA, Uduman M, Durham SR, Kleinstein SH, et al. Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis. J Allergy Clin Immunol. 2014;134(3):604–12 A study performed in AR subjects and control that exploits next-generation sequencing to determine local and peripheral blood immunoglobulin heavy-chain gene (IGH) repertoires in patients with respiratory allergic disease, demonstrating that natural pollen exposure was associated with changes in IgE repertoires suggestive of ongoing germinal center reactions. These changes were more apparent in nasal biopsy specimens compared with peripheral blood and in patients with AR compared with healthy control subjects. PubMedPubMedCentralGoogle Scholar
  33. 33.
    • Ramadani F, Hobson P, Chan YC, Mzinza D, Bowen H, et al. Intrinsic properties of germinal center-derived B cells promote their enhanced class switching to IgE. Allergy. 2015;70(10):1269–77 This article studies the relation between the phenotypic composition of tonsil B cells and the CSR to IgE ex vivo. Naïve, germinal center (GC), early GC (eGC), and memory tonsil B cells were isolated from tonsils. This study shows that the maturation state of tonsil B cells determines their capacity to undergo class switching to IgE ex vivo, with the GC-derived B cells yielding the highest percentage of IgE(+) cells. PubMedPubMedCentralGoogle Scholar
  34. 34.
    Rondón C, Eguiluz-Gracia I, Campo P. Is the evidence of local allergic rhinitis growing? Curr Opin Allergy Clin Immunol. 2018;18(4):342–9.PubMedGoogle Scholar
  35. 35.
    Rondon C, Campo P, Togias A, Fokkens WJ, Durham SR, Powe DG, et al. Local allergic rhinitis: concept, pathophysiology, and management. J Allergy Clin Immunol. 2012;129(6):1460–7.PubMedGoogle Scholar
  36. 36.
    • Rondon C, Eguiluz-Gracia I, Plaza C, Bogas G, Galindo P, Mayorga C, et al. Local allergic rhinitis is an independent rhinitis phenotype: the results of a 10-year follow-up study. Allergy. 2018;73(2):470–8 This study is the second phase of a 10-year follow-up study of a cohort of 176 patients with LAR and 115 age- and sex-matched healthy controls. The aim of this study was to prospectively evaluate the natural history of a population with LAR, the potential conversion to AR with systemic atopy and the development of asthma. After 10-year LAR, patients experienced a significant worsening of the rhinitis, with increase in emergency assistance, development of asthma, loss of allergen tolerance, and impairment of the quality of life. A similar rate of development of AR with systemic atopy was detected in patients and controls. PubMedGoogle Scholar
  37. 37.
    Lopez S, Rondon C, Torres MJ, Campo P, Canto G, Fernandez R, et al. Immediate and dual response to nasal challenge with Dermatophagoides pteronyssinus in local allergic rhinitis. Clin Exp Allergy. 2010;40(7):1007–14.PubMedGoogle Scholar
  38. 38.
    Huggins KG, Brostoff J. Local production of specific IgE antibodies in allergic-rhinitis patients with negative skin tests. Lancet. 1975;2(7926):148–50.PubMedGoogle Scholar
  39. 39.
    Powe DG, Jagger C, Kleinjan A, Carney AS, Jenkins D, Jones NS. ‘Entopy’: localized mucosal allergic disease in the absence of systemic responses for atopy. Clin Exp Allergy. 2003;33(10):1374–9.PubMedGoogle Scholar
  40. 40.
    Rondon C, Dona I, Lopez S, Campo P, Romero JJ, Torres MJ, et al. Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response. Allergy. 2008;63(10):1352–8.PubMedGoogle Scholar
  41. 41.
    Fuiano N, Fusilli S, Incorvaia C. A role for measurement of nasal IgE antibodies in diagnosis of Alternaria-induced rhinitis in children. Allergol Immunopathol (Madr). 2012;40(2):71–4 P.Google Scholar
  42. 42.
    • Zicari AM, Occasi F, Di Fraia M, Mainiero F, Porzia A, Galandrini R, et al. Local allergic rhinitis in children: novel diagnostic features and potential biomarkers. Am J Rhinol Allergy. 2016;30(5):329–34 Study performed in 20 children with negative skin-prick test and serum specific immunoglobulin E. NAPT with dust mite and grass pollen was performed, and slgE, IL-5, and TSLP was measured in nasal lavage. NAPT was positive in 12 children (66.7%). Nasal slgE for allergens ( D. pteronyssinus , D. farinae, Lolium perenne ), IL-5, and TSLP levels increased significantly after NAPT. PubMedGoogle Scholar
  43. 43.
    • Krajewska-Wojtys A, Jarzab J, Gawlik R, Bozek A. Local allergic rhinitis to pollens is underdiagnosed in young patients. Am J Rhinol Allergy. 2016;30(6):198–201 A study was performed in 121 young patients (12–18 years old) with SPT/sIgE and typical seasonal nasal symptoms were examined. NPT and nasal-specific immunoglobulin E were performed. LAR to grass pollen ( P. pratense ), Artemisia, and birch was confirmed in 17 (16.6%), 6 (5.9%), and 9 (8.9%) patients, respectively. Concentrations of nasal IgE were similar among the analyzed groups. PubMedGoogle Scholar
  44. 44.
    Buntarickpornpan P, Veskitkul J, Pacharn P, Visitsunthorn N, Vichyanond P, Tantilipikorn P, et al. The proportion of local allergic rhinitis to Dermatophagoides pteronyssinus in children. Pediatr Allergy Immunol. 2016;27(6):574–9.PubMedGoogle Scholar
  45. 45.
    Rondon C, Blanca-Lopez N, Aranda A, Herrera R, Rodriguez-Bada JL, Canto G, et al. Local allergic rhinitis: allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen. J Allergy Clin Immunol. 2011;127(4):1069–71.PubMedGoogle Scholar
  46. 46.
    Rondon C, Campo P, Salas M, Aranda A, Molina A, Gonzalez M, et al. Efficacy and safety of D. pteronyssinus immunotherapy in local allergic rhinitis: a double-blind placebo-controlled clinical trial. Allergy. 2016;71(7):1057–61.PubMedGoogle Scholar
  47. 47.
    Bożek A, Jarząb J. Efficacy and safety of birch pollen immunotherapy for local allergic rhinitis. Ann Allergy Asthma Immunol. 2018;120(1):53–8.PubMedGoogle Scholar
  48. 48.
    •• Rondón C, Blanca-Lopez N, Campo P, Mayorga C, Jurado-Escobar R, Torres MJ, et al. Specific immunotherapy in local allergic rhinitis: a randomized, double-blind placebo-controlled trial with Phleum pratense subcutaneous allergen immunotherapy. Allergy. 2018;73(4):905–15 A randomized double-blind placebo-controlled study in 56 patients with moderate-severe LAR to grass pollen, where patients received pollen immunotherapy (IT) or placebo for the first year, and pollen immunotherapy during the second one. IT had a short-term and sustained effect with significant improvements of all primary and secondary clinical outcomes, with increased serum sIgG4 levels and allergen tolerance, with no severe adverse events reported. PubMedGoogle Scholar
  49. 49.
    Jayaratnam A, Corrigan CJ, Lee TH. The continuing enigma of non-atopic asthma. Clin Exp Allergy. 2005;35(7):835–7.PubMedGoogle Scholar
  50. 50.
    Humbert M, 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(5):1497–504.PubMedGoogle Scholar
  51. 51.
    Humbert M, 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. 1996;153(6 Pt 1):1931–7.Google Scholar
  52. 52.
    Bentley AM, Durham SR, Kay AB. Comparison of the immunopathology of extrinsic, intrinsic and occupational asthma. J Investig Allergol Clin Immunol. 1994;4(5):222–32.PubMedGoogle Scholar
  53. 53.
    Humbert M, Ying S, Corrigan C, Menz G, Barkans J, Pfister R, et al. Bronchial mucosal expression of the genes encoding chemokines RANTES and MCP-3 in symptomatic atopic and nonatopic asthmatics: relationship to the eosinophil-active cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor, and IL-3. Am J Respir Cell Mol Biol. 1997;16(1):1–8.PubMedGoogle Scholar
  54. 54.
    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(6 Pt 1):1931–7.PubMedGoogle Scholar
  55. 55.
    Balzar S, Rhodes D, Wenzel SE. IgE expression pattern in lung: relation to systemic IgE and asthma phenotypes. J Allergy Clin Immunol. 2007;119(4):855–62.PubMedPubMedCentralGoogle Scholar
  56. 56.
    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(2):206–14.PubMedGoogle Scholar
  57. 57.
    Pillai P, Fang C, Chan YC, Shamji MH, Harper C, Wu SY, et al. Allergen-specific IgE is not detectable in the bronchial mucosa of nonatopic asthmatic patients. J Allergy Clin Immunol. 2014;133(6):1770–2 e11.PubMedGoogle Scholar
  58. 58.
    Bachert C, Holtappels G, De Lobel L, van Cauwenberge P, Liu S, Lin P, et al. Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma. J Allergy Clin Immunol. 2010;126(5):962–8.PubMedGoogle Scholar
  59. 59.
    Van Zele T, Holtappels G, van Cauwenberge P, Bachert C. Local immunoglobulin production in nasal polyposis is modulated by superantigens. Clin Exp Allergy. 2007;37:1840–7.PubMedGoogle Scholar
  60. 60.
    Gevaert P, Johansson SG, Cuvelier C, Cauwenberge P, Bachert C. Organization of secondary lymphoid tissue and local IgE formation to Staphylococcus aureus enterotoxins in nasal polyp tissue. Allergy. 2005;60:71–9.PubMedGoogle Scholar
  61. 61.
    Groot Kormelink T, Calus L, De Ruyck N, Holtappels G, Bachert C, Redegeld FA, et al. Local free light chain expression is increased in chronic rhinosinusitis with nasal polyps. Allergy. 2012;67(9):1165–72.PubMedGoogle Scholar
  62. 62.
    • Baba S, Toma-Hirano M, Kanaya K, Suzukawa K, Ushio M, Suzukawa M, et al. Local increase in IgE and class switch recombination to IgE in nasal polyps in chronic rhinosinusitis. Clin Exp Allergy. 2014;44(5):701–12 Local IgE production and class switch recombination to IgE were assessed in two subtypes of chronic rhinosinusitis with nasal polyps (eosinophilic and non-eosinophilic chronic rhinosinusitis). This study demonstrates local class switching to IgE, production of IgE, and IgE localization to the surface of mast cells in eosinophilic chronic rhinosinusitis in Japanese population. PubMedGoogle Scholar
  63. 63.
    Bachert C. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE ‘above atopy’. J Intern Med. 2012;272(2):133–43.PubMedGoogle Scholar
  64. 64.
    Bozek A, Ignasiak B, Kasperska-Zajac A, Scierski W, Grzanka A, Jarzab J. Local allergic rhinitis in elderly patients. Ann Allergy Asthma Immunol. 2015;114(3):199–202.PubMedGoogle Scholar
  65. 65.
    Ota Y, Sato T, Funakoshi T, Hiruta N, Kitamura M, Bujo H, et al. Measuring local immunoglobulin E in the inferior turbinate nasal mucosa in patients with allergic rhinitis. Allergol Int. 2016;65(4):396–9.PubMedGoogle Scholar
  66. 66.
    Yoshida T, Kusumi T, Inafuku S, Sugiyama T, Koide N, Yokochi T. A quantitative analysis of cedar pollen-specific immunoglobulins in nasal lavage supported the local production of specific IgE, not of specific IgG. Microbiol Immunol. 2005;49(6):529–34.PubMedGoogle Scholar
  67. 67.
    Sakaida H, Takeuchi K. Measurement of Japanese cedar pollen-specific IgE in nasal secretions. Allergol Int. 2014;63(3):467–73.PubMedGoogle Scholar
  68. 68.
    Reisacher WR. Detecting local immunoglobulin E from mucosal brush biopsy of the inferior turbinates using microarray analysis. Int Forum Allergy Rhinol. 2013;3(5):399–403.PubMedGoogle Scholar
  69. 69.
    Nakagomi T, Tominaga T, Yamaki M, Hisamatsu S, Nakagomi O. Is atopy increasing? Lancet. 1994;343(8889):121–2.PubMedGoogle Scholar
  70. 70.
    Shamji MH, Durham SR. Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers. J Allergy Clin Immunol. 2017;140(6):1485–98.PubMedGoogle Scholar
  71. 71.
    Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131(5):1288–96 e3.PubMedGoogle Scholar
  72. 72.
    Calderon MA, Casale T, Cox L, Akdis CA, Burks AW, Nelson HS, et al. Allergen immunotherapy: a new semantic framework from the European Academy of Allergy and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL consensus report. Allergy. 2013;68(7):825–8.PubMedGoogle Scholar
  73. 73.
    Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1–55.PubMedGoogle Scholar
  74. 74.
    •• Shamji MH, Kappen JH, Akdis M, Jensen-Jarolim E, Knol EF, Kleine-Tebbe J, et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI position paper. Allergy. 2017;72(8):1156–73 Thorough review of candidate biomarkers used in clinical trials of AR patients. This group of experts recommends exploring the use of allergen-specific IgG4 as a biomarker for compliance, while sIgE/tIgE and IgE-FAB are considered potential surrogate candidate biomarkers. Cytokine/chemokines and cellular responses provide insight into the mechanisms of AIT. PubMedGoogle Scholar
  75. 75.
    Pfaar O, Demoly P, Gerth van Wijk R, Bonini S, Bousquet J, Canonica GW, et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI position paper. Allergy. 2014;69(7):854–67.PubMedGoogle Scholar
  76. 76.
    Szeinbach SL, Muntendam P, O’Connor RD. Identification of allergic disease among users of antihistamines. J Manag Care Pharm. 2004;10(3):234–8.PubMedGoogle Scholar
  77. 77.
    Chang ML, Liu YH, Pei LC, Shao B. Analysis of total immunoglobulin E and specific immunoglobulin E of 3,721 patients with allergic disease. Biomed Rep J. 2015;3(4):573–7.Google Scholar
  78. 78.
    Shamji MH, Ljorring C, Francis JN, Calderon MA, Larche M, Kimber I, et al. Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy. 2012;67(2):217–26.PubMedGoogle Scholar
  79. 79.
    Berings M, Gevaert P, De Ruyck N, Derycke L, Holtappels G, Pilette C et al. FcεRI expression and IgE binding by dendritic cells and basophils in allergic rhinitis and upon allergen immunotherapy. Clin Exp Allergy. 2018 Aug;48(8):970-980. Scholar
  80. 80.
    Gleich GJ, Zimmermann EM, Henderson LL, Yunginger JW. Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study. J Allergy Clin Immunol. 1982;70(4):261–71.PubMedGoogle Scholar
  81. 81.
    Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK, et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol. 2004;172(5):3252–9.PubMedGoogle Scholar
  82. 82.
    Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, et al. Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol. 2007;178(7):4658–66.PubMedGoogle Scholar
  83. 83.
    • Wollmann E, Kundi M, Selb R, Niederberger V, Valenta R. Reduction in allergen-specific IgE binding as measured by microarray: a possible surrogate marker for effects of specific immunotherapy. J Allergy Clin Immunol. 2015;136(3):806–9 e7. A study investigating the influence of AIT-induced allergen sIgG antibodies on IgE binding in microarray and CAP assays, and an association of IgE levels with clinical parameters. Samples were obtained in a double-blind placebo-controlled immunotherapy trial with recombinant hypoallergenic Bet v 1 derivatives before and after treatment. Results showed that allergen microarrays are useful to monitor the development of allergen-specific IgG responses during AIT, and the reduction in allergen-specific IgE binding measured by microarray analysis may be a useful surrogate marker for clinical effects of AIT. PubMedPubMedCentralGoogle Scholar
  84. 84.
    Ha EK, Lee S, Baek H, Lee SJ, Sheen YH, Jung YH, et al. Prevalence and clinical characteristics of local allergic rhinitis in children sensitized to house dust mites. Int Arch Allergy Immunol. 2017;174(3–4):183–9.PubMedGoogle Scholar
  85. 85.
    Jung CG, Ban GY, Park HS, Shin YS. Prevalence and clinical characteristics of local allergic rhinitis to house dust mites. Yonsei Med J. 2017;58(5):1047–50.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Tao XY, Chen D, Lin ZB, Wu SL, Liang MJ, Li CW, et al. Clinical characteristics and allergen sensitization patterns of patients with local allergic rhinitis in Southern China. Int Arch Allergy Immunol. 2018;175(1–2):107–13.PubMedGoogle Scholar
  87. 87.
    Ahn JY, Choi BS. Clinical evaluation of techniques for measuring nasal-specific immunoglobulin E in pediatric patients. J Korean Med Sci. 2017;32(12):2005–8.PubMedPubMedCentralGoogle Scholar
  88. 88.
    • Duman H, Bostanci I, Ozmen S, Dogru M. The relevance of nasal provocation testing in children with nonallergic rhinitis. Int Arch Allergy Immunol. 2016;170(2):115–21 A study performed in 28 children with symptoms suggestive of allergic rhinitis and negative SPT/sIgE and 30 healthy children. NPTs with grass mix, Dermatophagoides pteronyssinus, and D. farinae were performed, being positive in 7 (25%) patients. The study emphasizes that the diagnosis of LAR should be taken into consideration by pediatricians and pediatric allergy specialists. PubMedGoogle Scholar
  89. 89.
    ELBadawy NE, El-Anwar MW. Assessment of nasal immunoglobulin E level in atopic and non-atopic rhinitis patients: a tool for diagnosis of local allergic rhinitis. Egypt J Immunol. 2016;23(1):45–56.PubMedGoogle Scholar
  90. 90.
    Krajewska-Wojtys A, Zawadzińska K, Pyrkosz K, Bozek A. Local allergic rhinitis in adult patients with chronic nasal symptoms. Int Arch Allergy Immunol. 2017;173(3):165–70.PubMedGoogle Scholar
  91. 91.
    Campo P, Eguiluz-Gracia I, Bogas G, Salas M, Plaza Serón C, Pérez N, et al. Local allergic rhinitis: Implications for management. Clin Exp Allergy. 2018 Jun.
  92. 92.
    • Becker S, Eder K, Berghaus A, Kramer MF, Gröger M. Non-allergic rhinitis with eosinophilia syndrome is not associated with local production of specific IgE in nasal mucosa. Eur Arch Otorhinolaryngol. 2016;273(6):1469–75 Sera and nasal secretion of patients with NARES (perennial nasal symptoms, no evidence of acute or chronic rhinosinusitis with or without polyps, negative skin prick test, and eosinophilic cationic protein in nasal secretion >200 ng/ml) were tested by immunoassay-biochip technology (ImmunoCAP ® ISAC, Phadia) (112 allergen components). All results were negative demonstrating that NARES is not associated with local allergy (entopy). PubMedGoogle Scholar
  93. 93.
    Tao XY, Chen D, Lin ZB, Wu SL, Liang MJ, Li CW, et al. Clinical characteristics and allergen sensitization patterns of patients with local allergic rhinitis in Southern China. Int Arch Allergy Immunol. 2018;175(1–2):107–13.PubMedGoogle Scholar
  94. 94.
    Colavita L, Sposito G, Loddo S, Galletti B, Salpietro C, Galletti F, et al. Local allergic rhinitis in pediatric patients: is IgE dosage in nasal lavage fluid a useful diagnostic method in children? Int J Mol Cell Med. 2017;6(3):174–82.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Reisacher WR. Total and allergen-specific immunoglobulin E in the serum and nasal mucosa of a nonallergic population. Int Forum Allergy Rhinol. 2016;6(6):618–23.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Carmen Rondón
    • 1
  • Ibon Eguíluz-Gracia
    • 1
  • Mohamed H. Shamji
    • 2
  • Janice A. Layhadi
    • 2
  • María Salas
    • 1
  • María José Torres
    • 1
  • Paloma Campo
    • 1
    • 3
    Email author
  1. 1.Allergy UnitIBIMA-Regional University Hospital of MálagaMálagaSpain
  2. 2.Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and DevelopmentMRC Asthma UK Centre Imperial College LondonLondonUK
  3. 3.Plaza Hospital CivilMálagaSpain

Personalised recommendations