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Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 2, pp 190–204 | Cite as

The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses

  • Sayantani B. Sindher
  • Andrew Long
  • Swati Acharya
  • Vanitha Sampath
  • Kari C. Nadeau
Article

Abstract

The incidence of allergic conditions has continued to rise over the past several decades, with a growing body of research dedicated toward the treatment of such conditions. By driving a complex range of changes in the underlying immune response, immunotherapy is the only therapy that modulates the immune system with long-term effects and is presently utilized for the treatment of several atopic conditions. Recent efforts have focused on identifying biomarkers associated with these changes that may be of use in predicting patients with the highest likelihood of positive clinical outcomes during allergen immunotherapy (AIT), providing guidance regarding AIT discontinuation, and predicting symptomatic relapse and the need for booster AIT after therapy. The identification of such biomarkers in food allergy has the additional benefit of replacing oral food challenges, which are presently the gold standard for diagnosing food allergies. While several markers have shown early promise, research has yet to identify a marker that can invariably predict clinical response to AIT. Skin prick testing (SPT) and specific IgE have commonly been used as inclusion criteria for the initiation of AIT and prediction of reactions during subsequent allergen challenge; however, existing data suggests that changes in these markers are not always associated with clinical improvement and can be widely variable, reducing their utility in predicting clinical response. Similar findings have been described for the use of allergen-specific functional IgG4 antibodies, basophil activation and histamine release, and type 2 innate lymphoid cells. There appears to be a promising association between changes in the expression of dendritic cell-associated markers, as well as the use of DNA promoter region methylation patterns in the prediction of allergy status following therapy. The cellular and molecular changes brought about by immunotherapy are still under investigation, but major strides in our understanding are being made.

Keywords

Biomarkers Immunotherapy Prognostic Allergen Food allergy 

Notes

Acknowledgements

This work was supported by NIH grant U19AI104209, the Bezos Family Foundation, the FARE Center of Excellence, the Myra Reinhard Foundation, and the Sean N. Parker Center for Allergy and Asthma Research at Stanford University.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, Nelson M, Weber R, Bernstein DI, Blessing-Moore J (2011) Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 127:S1–55.  https://doi.org/10.1016/j.jaci.2010.09.034 CrossRefPubMedGoogle Scholar
  2. 2.
    Bousquet J, Schunemann HJ, Samolinski B et al (2012) Allergic rhinitis and its impact on asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol 130:1049–1062.  https://doi.org/10.1016/j.jaci.2012.07.053 CrossRefPubMedGoogle Scholar
  3. 3.
    Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S (2007) Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev:Cd001936.  https://doi.org/10.1002/14651858.CD001936.pub2
  4. 4.
    Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Klimek L, Knecht R, Stephan V, Tholstrup B, Weisshaar C, Kaiser F (2009) Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J allergy Clin Immunol 123:167-173.e167.  https://doi.org/10.1016/j.jaci.2008.10.044 CrossRefGoogle Scholar
  5. 5.
    Eifan AO, Akkoc T, Yildiz A, Keles S, Ozdemir C, Bahceciler NN, Barlan IB (2010) Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy 40:922–932.  https://doi.org/10.1111/j.1365-2222.2009.03448.x CrossRefPubMedGoogle Scholar
  6. 6.
    Powell RJ, Frew AJ, Corrigan CJ, Durham SR (2007) Effect of grass pollen immunotherapy with Alutard SQ on quality of life in seasonal allergic rhinoconjunctivitis. Allergy 62:1335–1338.  https://doi.org/10.1111/j.1398-9995.2007.01455.x CrossRefPubMedGoogle Scholar
  7. 7.
    Demoly P, Okamoto Y, Yang WH, Devillier P, Bergmann KC (2016) 300 IR HDM tablet: a sublingual immunotherapy tablet for the treatment of house dust mite-associated allergic rhinitis. Expert Rev Clin Immunol 12:1141–1151.  https://doi.org/10.1080/1744666x.2016.1237288 CrossRefPubMedGoogle Scholar
  8. 8.
    Shamji MH, Layhadi JA, Scadding GW, Cheung DK, Calderon MA, Turka LA, Phippard D, Durham SR (2015) Basophil expression of diamine oxidase: a novel biomarker of allergen immunotherapy response. J Allergy Clin Immunol 135:913-921.e919.  https://doi.org/10.1016/j.jaci.2014.09.049 Google Scholar
  9. 9.
    Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, Till SJ, Hamid QA, Nouri-Aria KT (1999) Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 341:468–475.  https://doi.org/10.1056/nejm199908123410702 CrossRefPubMedGoogle Scholar
  10. 10.
    Kouser L, Kappen J, Walton RP, Shamji MH (2017) Update on biomarkers to monitor clinical efficacy response during and post treatment in allergen immunotherapy. Curr Treat Options Allergy 4:43–53.  https://doi.org/10.1007/s40521-017-0117-5 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bousquet J, Lockey R, Malling HJ (1998) Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 102:558–562CrossRefGoogle Scholar
  12. 12.
    Bousquet J, Lockey R, Malling HJ, Alvarez-Cuesta E, Canonica GW, Chapman MD, Creticos PJ, Dayer JM, Durham SR, Demoly P, Goldstein RJ, Ishikawa T, Ito K, Kraft D, Lambert PH, Lowenstein H, Muller U, Norman PS, Reisman RE, Valenta R, Valovirta E, Yssel H (1998) Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American Academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 81:401–405CrossRefGoogle Scholar
  13. 13.
    Bussmann C, Bockenhoff A, Henke H, Werfel T, Novak N (2006) Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis? J Allergy Clin Immunol 118:1292–1298.  https://doi.org/10.1016/j.jaci.2006.07.054 CrossRefPubMedGoogle Scholar
  14. 14.
    Akdis CA, Akdis M (2015) Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organ J 8:17.  https://doi.org/10.1186/s40413-015-0063-2 CrossRefPubMedGoogle Scholar
  15. 15.
    Chinthrajah RS, Hernandez JD, Boyd SD, Galli SJ, Nadeau KC (2016) Molecular and cellular mechanisms of food allergy and food tolerance. J Allergy Clin Immunol 137:984–997.  https://doi.org/10.1016/j.jaci.2016.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Fuchs O, Bahmer T, Rabe KF, von Mutius E (2017) Asthma transition from childhood into adulthood. Lancet Respir Med 5:224–234.  https://doi.org/10.1016/s2213-2600(16)30187-4 CrossRefPubMedGoogle Scholar
  17. 17.
    Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, Hoetzenecker W, Knol E, Simon HU, Wollenberg A, Bieber T, Lauener R, Schmid-Grendelmeier P, Traidl-Hoffmann C, Akdis CA (2016) Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol 138:336–349.  https://doi.org/10.1016/j.jaci.2016.06.010 CrossRefPubMedGoogle Scholar
  18. 18.
    Palomares O, Akdis M, Martin-Fontecha M, Akdis CA (2017) Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells. Immunol Rev 278:219–236.  https://doi.org/10.1111/imr.12555 CrossRefPubMedGoogle Scholar
  19. 19.
    Zissler UM, Esser-von Bieren J, Jakwerth CA, Chaker AM, Schmidt-Weber CB (2016) Current and future biomarkers in allergic asthma. Allergy 71:475–494.  https://doi.org/10.1111/all.12828 CrossRefPubMedGoogle Scholar
  20. 20.
    Agache I, Akdis CA (2016) Endotypes of allergic diseases and asthma: an important step in building blocks for the future of precision medicine. Allergol Int 65:243–252.  https://doi.org/10.1016/j.alit.2016.04.011 CrossRefPubMedGoogle Scholar
  21. 21.
    Shamji MH, Durham SR (2011) Mechanisms of immunotherapy to aeroallergens. Clin Exp Allergy 41:1235–1246.  https://doi.org/10.1111/j.1365-2222.2011.03804.x CrossRefPubMedGoogle Scholar
  22. 22.
    Akdis CA, Akdis M (2015) Advances in allergen immunotherapy: aiming for complete tolerance to allergens. Sci Transl Med 7:280ps286.  https://doi.org/10.1126/scitranslmed.aaa7390 CrossRefGoogle Scholar
  23. 23.
    Lloyd CM, Saglani S (2013) T cells in asthma: influences of genetics, environment, and T-cell plasticity. J Allergy Clin Immunol 131:1267–1274; quiz 1275.  https://doi.org/10.1016/j.jaci.2013.02.016 CrossRefPubMedGoogle Scholar
  24. 24.
    Akdis CA (2012) Therapies for allergic inflammation: refining strategies to induce tolerance. Nat Med 18:736–749.  https://doi.org/10.1038/nm.2754 CrossRefPubMedGoogle Scholar
  25. 25.
    Galli SJ, Tsai M (2012) IgE and mast cells in allergic disease. Nat Med 18:693–704.  https://doi.org/10.1038/nm.2755 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Xiao C, Puddicombe SM, Field S et al. (2011) Defective epithelial barrier function in asthma. J Allergy Clin Immunol 128:549-556.e541-512.  https://doi.org/10.1016/j.jaci.2011.05.038 CrossRefGoogle Scholar
  27. 27.
    Palomares O, Martin-Fontecha M, Lauener R, Traidl-Hoffmann C, Cavkaytar O, Akdis M, Akdis CA (2014) Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-beta. Genes Immun 15:511–520.  https://doi.org/10.1038/gene.2014.45 CrossRefPubMedGoogle Scholar
  28. 28.
    Wawrzyniak P, Akdis CA, Finkelman FD, Rothenberg ME (2016) Advances and highlights in mechanisms of allergic disease in 2015. J Allergy Clin Immunol 137:1681–1696.  https://doi.org/10.1016/j.jaci.2016.02.010 CrossRefPubMedGoogle Scholar
  29. 29.
    Wawrzyniak P, Wawrzyniak M, Wanke K, Sokolowska M, Bendelja K, Rückert B, Globinska A, Jakiela B, Kast JI, Idzko M, Akdis M, Sanak M, Akdis CA (2017) Regulation of bronchial epithelial barrier integrity by type 2 cytokines and histone deacetylases in asthmatic patients. J Allergy Clin Immunol 139:93–103.  https://doi.org/10.1016/j.jaci.2016.03.050 CrossRefPubMedGoogle Scholar
  30. 30.
    Hammad H, Lambrecht BN (2015) Barrier epithelial cells and the control of type 2 immunity. Immunity 43:29–40.  https://doi.org/10.1016/j.immuni.2015.07.007 CrossRefPubMedGoogle Scholar
  31. 31.
    Morita H, Moro K, Koyasu S (2016) Innate lymphoid cells in allergic and nonallergic inflammation. J Allergy Clin Immunol 138:1253–1264.  https://doi.org/10.1016/j.jaci.2016.09.011 CrossRefPubMedGoogle Scholar
  32. 32.
    Doherty TA, Baum R, Newbury RO, Yang T, Dohil R, Aquino M, Doshi A, Walford HH, Kurten RC, Broide DH, Aceves S (2015) Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis. J Allergy Clin Immunol 136:792-794.e793.  https://doi.org/10.1016/j.jaci.2015.05.048 CrossRefGoogle Scholar
  33. 33.
    Mjosberg J, Spits H (2016) Human innate lymphoid cells. J Allergy Clin Immunol 138:1265–1276.  https://doi.org/10.1016/j.jaci.2016.09.009 CrossRefPubMedGoogle Scholar
  34. 34.
    Nagakumar P, Denney L, Fleming L, Bush A, Lloyd CM, Saglani S (2016) Type 2 innate lymphoid cells in induced sputum from children with severe asthma. J Allergy Clin Immunol 137:624-626.e626.  https://doi.org/10.1016/j.jaci.2015.06.038 CrossRefGoogle Scholar
  35. 35.
    Morita H, Arae K, Unno H, Miyauchi K, Toyama S, Nambu A, Oboki K, Ohno T, Motomura K, Matsuda A, Yamaguchi S, Narushima S, Kajiwara N, Iikura M, Suto H, McKenzie ANJ, Takahashi T, Karasuyama H, Okumura K, Azuma M, Moro K, Akdis CA, Galli SJ, Koyasu S, Kubo M, Sudo K, Saito H, Matsumoto K, Nakae S (2015) An interleukin-33–mast cell–interleukin-2 axis suppresses papain-induced allergic inflammation by promoting regulatory T cell numbers. Immunity 43:175–186.  https://doi.org/10.1016/j.immuni.2015.06.021 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Basinski TM, Holzmann D, Eiwegger T, Zimmermann M, Klunker S, Meyer N, Schmid-Grendelmeier P, Jutel M, Akdis CA (2009) Dual nature of T cell-epithelium interaction in chronic rhinosinusitis. J Allergy Clin Immunol 124:74-80.e71-78.  https://doi.org/10.1016/j.jaci.2009.04.019 CrossRefGoogle Scholar
  37. 37.
    Rebane A, Zimmermann M, Aab A, Baurecht H, Koreck A, Karelson M, Abram K, Metsalu T, Pihlap M, Meyer N, Fölster-Holst R, Nagy N, Kemeny L, Kingo K, Vilo J, Illig T, Akdis M, Franke A, Novak N, Weidinger S, Akdis CA (2012) Mechanisms of IFN-gamma-induced apoptosis of human skin keratinocytes in patients with atopic dermatitis. J Allergy Clin Immunol 129:1297–1306.  https://doi.org/10.1016/j.jaci.2012.02.020 CrossRefPubMedGoogle Scholar
  38. 38.
    Finotto S, Neurath MF, Glickman JN, Qin S, Lehr HA, Green FH, Ackerman K, Haley K, Galle PR, Szabo SJ, Drazen JM, de Sanctis GT, Glimcher LH (2002) Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295:336–338.  https://doi.org/10.1126/science.1065544 CrossRefPubMedGoogle Scholar
  39. 39.
    Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, Martin B, Wilhelm C, Stockinger B (2008) Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 9:1341–1346.  https://doi.org/10.1038/ni.1659 CrossRefPubMedGoogle Scholar
  40. 40.
    Czarnowicki T, Gonzalez J, Shemer A et al. (2015) Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population. J allergy Clin Immunol 136:104-115.e107.  https://doi.org/10.1016/j.jaci.2015.01.020 PubMedGoogle Scholar
  41. 41.
    Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, Cianfarani F, Odorisio T, Traidl-Hoffmann C, Behrendt H, Durham SR, Schmidt-Weber CB, Cavani A (2009) Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 119:3573–3585.  https://doi.org/10.1172/jci40202 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Wegrzyn AS, Jakiela B, Ruckert B, Jutel M, Akdis M, Sanak M, Akdis CA (2015) T-cell regulation during viral and nonviral asthma exacerbations. J Allergy Clin Immunol 136:194-197.e199.  https://doi.org/10.1016/j.jaci.2014.12.1866 CrossRefGoogle Scholar
  43. 43.
    Noval Rivas M, Chatila TA (2016) Regulatory T cells in allergic diseases. J Allergy Clin Immunol 138:639–652.  https://doi.org/10.1016/j.jaci.2016.06.003 CrossRefPubMedGoogle Scholar
  44. 44.
    Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA (2010) Role of Treg in immune regulation of allergic diseases. Eur J Immunol 40:1232–1240.  https://doi.org/10.1002/eji.200940045 CrossRefPubMedGoogle Scholar
  45. 45.
    Yu W, Freeland DM, Nadeau KC (2016) Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol 16:751–765.  https://doi.org/10.1038/nri.2016.111 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Hussey Freeland DM, Fan-Minogue H, Spergel JM, Chatila TA, Nadeau KC (2016) Advances in food allergy oral immunotherapy: toward tolerance. Curr Opin Immunol 42:119–123.  https://doi.org/10.1016/j.coi.2016.08.002 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Moingeon P (2016) Biomarkers for allergen immunotherapy: a "panoromic" view. Immunol Allergy Clin N Am 36:161–179.  https://doi.org/10.1016/j.iac.2015.08.004 CrossRefGoogle Scholar
  48. 48.
    Moingeon P, Mascarell L (2012) Novel routes for allergen immunotherapy: safety, efficacy and mode of action. Immunotherapy 4:201–212.  https://doi.org/10.2217/imt.11.171 CrossRefPubMedGoogle Scholar
  49. 49.
    Passalacqua G, Compalati E, Canonica GW (2011) Sublingual immunotherapy: other indications. Immunol Allergy Clin N Am 31(279–287):ix–287.  https://doi.org/10.1016/j.iac.2011.02.011 CrossRefGoogle Scholar
  50. 50.
    Akdis M, Akdis CA (2014) Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol 133:621–631.  https://doi.org/10.1016/j.jaci.2013.12.1088 CrossRefPubMedGoogle Scholar
  51. 51.
    Kostadinova AI, Willemsen LE, Knippels LM, Garssen J (2013) Immunotherapy—risk/benefit in food allergy. Pediatr Allergy Immunol 24:633–644.  https://doi.org/10.1111/pai.12122 CrossRefPubMedGoogle Scholar
  52. 52.
    Nowak-Wegrzyn A, Fiocchi A (2010) Is oral immunotherapy the cure for food allergies? Curr Opin Allergy Clin Immunol 10:214–219.  https://doi.org/10.1097/ACI.0b013e3283399404 CrossRefPubMedGoogle Scholar
  53. 53.
    Rolinck-Werninghaus C, Staden U, Mehl A, Hamelmann E, Beyer K, Niggemann B (2005) Specific oral tolerance induction with food in children: transient or persistent effect on food allergy? Allergy 60:1320–1322.  https://doi.org/10.1111/j.1398-9995.2005.00882.x CrossRefGoogle Scholar
  54. 54.
    McGowan EC, Wood RA (2014) Sublingual (SLIT) versus oral immunotherapy (OIT) for food allergy. Curr Allergy Asthma Rep 14:486.  https://doi.org/10.1007/s11882-014-0486-9 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Mempel M, Rakoski J, Ring J, Ollert M (2003) Severe anaphylaxis to kiwi fruit: immunologic changes related to successful sublingual allergen immunotherapy. J Allergy Clin Immunol 111:1406–1409CrossRefGoogle Scholar
  56. 56.
    Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG, Mokhtarani M, Seyfert-Margolis V, Asare A, Bateman K, Deniz Y (2006) Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 117:134–140.  https://doi.org/10.1016/j.jaci.2005.09.036 CrossRefPubMedGoogle Scholar
  57. 57.
    Traister RS, Green TD, Mitchell L, Greenhawt M (2012) Community opinions regarding oral immunotherapy for food allergies. Ann Allergy Asthma Immunol 109:319–323.  https://doi.org/10.1016/j.anai.2012.08.012 CrossRefPubMedGoogle Scholar
  58. 58.
    Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT (2011) Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy. J Allergy Clin Immunol 127:1622–1624.  https://doi.org/10.1016/j.jaci.2011.04.009 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Mansfield L (2006) Successful oral desensitization for systemic peanut allergy. Ann Allergy Asthma Immunol 97:266–267.  https://doi.org/10.1016/s1081-1206(10)60026-9 CrossRefPubMedGoogle Scholar
  60. 60.
    Schneider LC, Rachid R, LeBovidge J, Blood E, Mittal M, Umetsu DT (2013) A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol 132:1368–1374.  https://doi.org/10.1016/j.jaci.2013.09.046 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Labrosse R, Graham F, Des Roches A, Begin P (2017) The use of omalizumab in food oral immunotherapy. Arch Immunol Ther Exp 65:189–199.  https://doi.org/10.1007/s00005-016-0420-z CrossRefGoogle Scholar
  62. 62.
    Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M, Bush RK, Metcalfe DD (1988) Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol 82:986–997CrossRefGoogle Scholar
  63. 63.
    Hill DJ, Heine RG, Hosking CS (2004) The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol 15:435–441.  https://doi.org/10.1111/j.1399-3038.2004.00188.x CrossRefPubMedGoogle Scholar
  64. 64.
    Kay AB (2001) Allergy and allergic diseases. First of two parts. N Engl J Med 344:30–37.  https://doi.org/10.1056/nejm200101043440106 CrossRefPubMedGoogle Scholar
  65. 65.
    Sporik R, Hill DJ, Hosking CS (2000) Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy 30:1540–1546CrossRefGoogle Scholar
  66. 66.
    Eigenmann PA, Sampson HA (1998) Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol 9:186–191CrossRefGoogle Scholar
  67. 67.
    Aas K, Backman A, Belin L, Weeke B (1978) Standardization of allergen extracts with appropriate methods. The combined use of skin prick testing and radio-allergosorbent tests. Allergy 33:130–137CrossRefGoogle Scholar
  68. 68.
    Dreborg S (2001) Histamine reactivity of the skin. Allergy 56:359–364CrossRefGoogle Scholar
  69. 69.
    Ueno H, Yoshioka K, Matsumoto T (2007) Usefulness of the skin index in predicting the outcome of oral challenges in children. J Investig Allergol Clin Immunol 17:207–210PubMedGoogle Scholar
  70. 70.
    van der Valk JP, Gerth van Wijk R, Hoorn E, Groenendijk L, Groenendijk IM, de Jong NW (2015) Measurement and interpretation of skin prick test results. Clin Transl Allergy 6:8.  https://doi.org/10.1186/s13601-016-0092-0 CrossRefPubMedGoogle Scholar
  71. 71.
    Ishizaka T, De Bernardo R, Tomioka H, Lichtenstein LM, Ishizaka K (1972) Identification of basophil granulocytes as a site of allergic histamine release. J Immunol 108:1000–1008PubMedGoogle Scholar
  72. 72.
    MacGlashan D Jr (2010) Expression of CD203c and CD63 in human basophils: relationship to differential regulation of piecemeal and anaphylactic degranulation processes. Clin Exp Allergy 40:1365–1377.  https://doi.org/10.1111/j.1365-2222.2010.03572.x CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Schroeder JT, Kagey-Sobotka A, Lichtenstein LM (1995) The role of the basophil in allergic inflammation. Allergy 50:463–472CrossRefGoogle Scholar
  74. 74.
    Shamji MH, Kappen JH, Akdis M, Jensen-Jarolim E, Knol EF, Kleine-Tebbe J, Bohle B, Chaker AM, Till SJ, Valenta R, Poulsen LK, Calderon MA, Demoly P, Pfaar O, Jacobsen L, Durham SR, Schmidt-Weber CB (2017) Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI position paper. Allergy 72:1156–1173.  https://doi.org/10.1111/all.13138 CrossRefPubMedGoogle Scholar
  75. 75.
    van Neerven RJ, Wikborg T, Lund G, Jacobsen B, Brinch-Nielsen A, Arnved J, Ipsen H (1999) Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation. J Immunol 163:2944–2952PubMedGoogle Scholar
  76. 76.
    Wachholz PA, Soni NK, Till SJ, Durham SR (2003) Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 112:915–922.  https://doi.org/10.1016/s0091 CrossRefPubMedGoogle Scholar
  77. 77.
    Kepley CL, Cambier JC, Morel PA, Lujan D, Ortega E, Wilson BS, Oliver JM (2000) Negative regulation of FcepsilonRI signaling by FcgammaRII costimulation in human blood basophils. J Allergy Clin Immunol 106:337–348CrossRefGoogle Scholar
  78. 78.
    Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, Stablein D, Henning AK, Vickery BP, Liu AH, Scurlock AM, Shreffler WG, Plaut M, Sampson HA, Consortium of Food Allergy Research (CoFAR) (2012) Oral immunotherapy for treatment of egg allergy in children. N Engl J Med 367:233–243.  https://doi.org/10.1056/NEJMoa1200435 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Gorelik M, Narisety SD, Guerrerio AL, Chichester KL, Keet CA, Bieneman AP, Hamilton RG, Wood RA, Schroeder JT, Frischmeyer-Guerrerio PA (2015) Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol 135:1283–1292.  https://doi.org/10.1016/j.jaci.2014.11.010 CrossRefPubMedGoogle Scholar
  80. 80.
    Jones SM, Pons L, Roberts JL et al. (2009) Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 124:292-300, 300.e291-297.  https://doi.org/10.1016/j.jaci.2009.05.022 CrossRefGoogle Scholar
  81. 81.
    Vickery BP, Scurlock AM, Kulis M, Steele PH, Kamilaris J, Berglund JP, Burk C, Hiegel A, Carlisle S, Christie L, Perry TT, Pesek RD, Sheikh S, Virkud Y, Smith PB, Shamji MH, Durham SR, Jones SM, Burks AW (2014) Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol 133:468–475.  https://doi.org/10.1016/j.jaci.2013.11.007 CrossRefPubMedGoogle Scholar
  82. 82.
    Buhring HJ, Streble A, Valent P (2004) The basophil-specific ectoenzyme E-NPP3 (CD203c) as a marker for cell activation and allergy diagnosis. Int Arch Allergy Immunol 133:317–329.  https://doi.org/10.1159/000077351 CrossRefPubMedGoogle Scholar
  83. 83.
    Knol EF, Mul FP, Jansen H, Calafat J, Roos D (1991) Monitoring human basophil activation via CD63 monoclonal antibody 435. J Allergy Clin Immunol 88:328–338CrossRefGoogle Scholar
  84. 84.
    Hennersdorf F, Florian S, Jakob A, Baumgartner K, Sonneck K, Nordheim A, Biedermann T, Valent P, Buhring HJ (2005) Identification of CD13, CD107a, and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-dependent upregulation. Cell Res 15:325–335.  https://doi.org/10.1038/sj.cr.7290301 CrossRefPubMedGoogle Scholar
  85. 85.
    Aasbjerg K, Backer V, Lund G, Holm J, Nielsen NC, Holse M, Wagtmann VR, Wurtzen PA (2014) Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy. Clin Exp Allergy 44:417–428CrossRefGoogle Scholar
  86. 86.
    Ceuppens JL, Bullens D, Kleinjans H, van der Werf J (2009) Immunotherapy with a modified birch pollen extract in allergic rhinoconjunctivitis: clinical and immunological effects. Clin Exp Allergy 39:1903–1909.  https://doi.org/10.1111/j.1365-2222.2009.03379.x CrossRefPubMedGoogle Scholar
  87. 87.
    Schmid JM, Wurtzen PA, Dahl R, Hoffmann HJ (2014) Early improvement in basophil sensitivity predicts symptom relief with grass pollen immunotherapy. J Allergy Clin Immunol 134:741-744.e745.  https://doi.org/10.1016/j.jaci.2014.04.029 CrossRefGoogle Scholar
  88. 88.
    Kepil Ozdemir S, Sin BA, Guloglu D, Ikinciogullari A, Gencturk Z, Misirligil Z (2014) Short-term preseasonal immunotherapy: is early clinical efficacy related to the basophil response? Int Arch Allergy Immunol 164:237–245.  https://doi.org/10.1159/000365628 CrossRefPubMedGoogle Scholar
  89. 89.
    Gokmen NM, Ersoy R, Gulbahar O, Ardeniz O, Sin A, Unsel M, Kokuludag A (2012) Desensitization effect of preseasonal seven-injection allergoid immunotherapy with olive pollen on basophil activation: the efficacy of olive pollen-specific preseasonal allergoid immunotherapy on basophils. Int Arch Allergy Immunol 159:75–82.  https://doi.org/10.1159/000335251 CrossRefPubMedGoogle Scholar
  90. 90.
    Lalek N, Kosnik M, Silar M, Korosec P (2010) Immunoglobulin G-dependent changes in basophil allergen threshold sensitivity during birch pollen immunotherapy. Clin Exp Allergy 40:1186–1193.  https://doi.org/10.1111/j.1365-2222.2010.03524.x CrossRefPubMedGoogle Scholar
  91. 91.
    Nopp A, Cardell LO, Johansson SG, Oman H (2009) CD-sens: a biological measure of immunological changes stimulated by ASIT. Allergy 64:811–814.  https://doi.org/10.1111/j.1398-9995.2008.01900.x CrossRefPubMedGoogle Scholar
  92. 92.
    Zidarn M, Kosnik M, Silar M, Bajrovic N, Korosec P (2015) Sustained effect of grass pollen subcutaneous immunotherapy on suppression of allergen-specific basophil response; a real-life, nonrandomized controlled study. Allergy 70:547–555.  https://doi.org/10.1111/all.12581 CrossRefPubMedGoogle Scholar
  93. 93.
    Gomez E, Fernandez TD, Dona I et al (2015) Initial immunological changes as predictors for house dust mite immunotherapy response. Clin Exp Allergy 45:1542–1553.  https://doi.org/10.1111/cea.12578 CrossRefPubMedGoogle Scholar
  94. 94.
    Syed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, Berglund JP, Tsai M, Maecker H, O’Riordan G, Galli SJ, Nadeau KC (2014) Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol 133:500–510.  https://doi.org/10.1016/j.jaci.2013.12.1037 CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Van Overtvelt L, Baron-Bodo V, Horiot S et al (2011) Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy. Allergy 66:1530–1537.  https://doi.org/10.1111/j.1398-9995.2011.02696.x CrossRefPubMedGoogle Scholar
  96. 96.
    MacGlashan DW, Jr., Savage JH, Wood RA, Saini SS (2012) Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors. J Allergy Clin Immunol 130:1130-1135.e1135.  https://doi.org/10.1016/j.jaci.2012.05.038 CrossRefGoogle Scholar
  97. 97.
    MacGlashan DW Jr (2007) Relationship between spleen tyrosine kinase and phosphatidylinositol 5′ phosphatase expression and secretion from human basophils in the general population. J Allergy Clin Immunol 119:626–633.  https://doi.org/10.1016/j.jaci.2006.09.040 CrossRefPubMedGoogle Scholar
  98. 98.
    MacGlashan DW, Jr., Saini SS (2017) Syk expression and IgE-mediated histamine release in basophils as biomarkers for predicting the clinical efficacy of omalizumab. J Allergy Clin Immunol 139:1680–1682 e1610.  https://doi.org/10.1016/j.jaci.2016.12.965 CrossRefGoogle Scholar
  99. 99.
    Ishmael S, MacGlashan D Jr (2009) Early signal protein expression profiles in basophils: a population study. J Leukoc Biol 86:313–325.  https://doi.org/10.1189/jlb.1208724 CrossRefPubMedGoogle Scholar
  100. 100.
    Artis D, Spits H (2015) The biology of innate lymphoid cells. Nature 517:293–301.  https://doi.org/10.1038/nature14189 CrossRefPubMedGoogle Scholar
  101. 101.
    Spits H, Cupedo T (2012) Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol 30:647–675.  https://doi.org/10.1146/annurev-immunol-020711-075053 CrossRefPubMedGoogle Scholar
  102. 102.
    Imai Y, Yasuda K, Sakaguchi Y, Haneda T, Mizutani H, Yoshimoto T, Nakanishi K, Yamanishi K (2013) Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice. Proc Natl Acad Sci U S A 110:13921–13926.  https://doi.org/10.1073/pnas.1307321110 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Hams E, Locksley RM, McKenzie AN, Fallon PG (2013) Cutting edge: IL-25 elicits innate lymphoid type 2 and type II NKT cells that regulate obesity in mice. J Immunol 191:5349–5353.  https://doi.org/10.4049/jimmunol.1301176 CrossRefPubMedGoogle Scholar
  104. 104.
    Kim BS, Siracusa MC, Saenz SA, Noti M, Monticelli LA, Sonnenberg GF, Hepworth MR, Van Voorhees AS, Comeau MR, Artis D (2013) TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Sci Transl Med 5:170ra116.  https://doi.org/10.1126/scitranslmed.3005374 CrossRefGoogle Scholar
  105. 105.
    Doherty TA, Scott D, Walford HH, Khorram N, Lund S, Baum R, Chang J, Rosenthal P, Beppu A, Miller M, Broide DH (2014) Allergen challenge in allergic rhinitis rapidly induces increased peripheral blood type 2 innate lymphoid cells that express CD84. J Allergy Clin Immunol 133:1203–1205.  https://doi.org/10.1016/j.jaci.2013.12.1086 CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Lao-Araya M, Steveling E, Scadding GW, Durham SR, Shamji MH (2014) Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol 134:1193-1195.e1194.  https://doi.org/10.1016/j.jaci.2014.07.029 CrossRefGoogle Scholar
  107. 107.
    Lombardi V, Beuraud C, Neukirch C, Moussu H, Morizur L, Horiot S, Luce S, Wambre E, Linsley P, Chollet-Martin S, Baron-Bodo V, Aubier M, Moingeon P (2016) Circulating innate lymphoid cells are differentially regulated in allergic and nonallergic subjects. J Allergy Clin Immunol 138:305–308.  https://doi.org/10.1016/j.jaci.2015.12.1325 CrossRefPubMedGoogle Scholar
  108. 108.
    Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, Nelson H, Akdis CA (2013) Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol 131:1288-1296.e1283.  https://doi.org/10.1016/j.jaci.2013.01.049 CrossRefGoogle Scholar
  109. 109.
    Calderon MA, Casale T, Cox L, Akdis CA, Burks AW, Nelson HS, Jutel M, Demoly P (2013) 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 68:825–828CrossRefGoogle Scholar
  110. 110.
    Cox LS, Casale TB, Nayak AS, Bernstein DI, Creticos PS, Ambroisine L, Melac M, Zeldin RK (2012) Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the importance of allergen-specific serum IgE. J Allergy Clin Immunol 130:1327–1334 e1321.  https://doi.org/10.1016/j.jaci.2012.08.032 CrossRefGoogle Scholar
  111. 111.
    Baron-Bodo V, Horiot S, Lautrette A, Chabre H, Drucbert AS, Danzé PM, Sénéchal H, Peltre G, Galvain S, Zeldin RK, Horak F, Moingeon P (2013) Heterogeneity of antibody responses among clinical responders during grass pollen sublingual immunotherapy. Clin Exp Allergy 43:1362–1373.  https://doi.org/10.1111/cea.12187 CrossRefPubMedGoogle Scholar
  112. 112.
    Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK, Staple SQ, Aalberse RC, Till SJ, Durham SR (2004) Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172:3252–3259CrossRefGoogle Scholar
  113. 113.
    Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, Francis JN, Durham SR (2007) Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol 178:4658–4666CrossRefGoogle Scholar
  114. 114.
    Chin SJ, Vickery BP, Kulis MD, Kim EH, Varshney P, Steele P, Kamilaris J, Hiegel AM, Carlisle SK, Smith PB, Scurlock AM, Jones SM, Burks AW (2013) Sublingual versus oral immunotherapy for peanut-allergic children: a retrospective comparison. J Allergy Clin Immunol 132:476–478 e472.  https://doi.org/10.1016/j.jaci.2013.02.017 CrossRefGoogle Scholar
  115. 115.
    Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, Steele P, Driggers S, Burks AW, Wood RA (2012) The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 129:448-455, 455 e441-445.  https://doi.org/10.1016/j.jaci.2011.10.023 CrossRefGoogle Scholar
  116. 116.
    Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, Gorelik M, Schroeder J, Hamilton RG, Wood RA (2015) A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol 135(1275–1282):e1271–e1276.  https://doi.org/10.1016/j.jaci.2014.11.005 CrossRefGoogle Scholar
  117. 117.
    Fleischer DM, Burks AW, Vickery BP, Scurlock AM, Wood RA, Jones SM, Sicherer SH, Liu AH, Stablein D, Henning AK, Mayer L, Lindblad R, Plaut M, Sampson HA, Consortium of Food Allergy Research (CoFAR) (2013) Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial. J Allergy Clin Immunol 131(119–127):e111–e117.  https://doi.org/10.1016/j.jaci.2012.11.011 CrossRefGoogle Scholar
  118. 118.
    Di Lorenzo G, Mansueto P, Pacor ML et al. (2009) Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy. J Allergy Clin Immunol 123:1103-1110, 1110.e1101-1104.  https://doi.org/10.1016/j.jaci.2009.02.012 CrossRefGoogle Scholar
  119. 119.
    Li Q, Li M, Yue W, Zhou J, Li R, Lin J, Li Y (2014) Predictive factors for clinical response to allergy immunotherapy in children with asthma and rhinitis. Int Arch Allergy Immunol 164:210–217.  https://doi.org/10.1159/000365630 CrossRefPubMedGoogle Scholar
  120. 120.
    Wurtzen PA, Lund G, Lund K, Arvidsson M, Rak S, Ipsen H (2008) A double-blind placebo-controlled birch allergy vaccination study II: correlation between inhibition of IgE binding, histamine release and facilitated allergen presentation. Clin Exp Allergy 38:1290–1301.  https://doi.org/10.1111/j.1365-2222.2008.03020.x CrossRefPubMedGoogle Scholar
  121. 121.
    Andorf S, Borres MP, Block W, Tupa D, Bollyky JB, Sampath V, Elizur A, Lidholm J, Jones JE, Galli SJ, Chinthrajah RS, Nadeau KC (2017) Association of clinical reactivity with sensitization to allergen components in multifood-allergic children. J Allergy Clin Immunol Pract 5:1325–1334.e4.  https://doi.org/10.1016/j.jaip.2017.01.016 CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Wood RA (2016) Food allergen immunotherapy: current status and prospects for the future. J Allergy Clin Immunol 137:973–982.  https://doi.org/10.1016/j.jaci.2016.01.001 CrossRefGoogle Scholar
  123. 123.
    Flicker S, Valenta R (2003) Renaissance of the blocking antibody concept in type I allergy. Int Arch Allergy Immunol 132:13–24CrossRefGoogle Scholar
  124. 124.
    Wachholz PA, Durham SR (2004) Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol 4:313–318CrossRefGoogle Scholar
  125. 125.
    Lupinek C, Wollmann E, Baar A, Banerjee S, Breiteneder H, Broecker BM, Bublin M, Curin M, Flicker S, Garmatiuk T, Hochwallner H, Mittermann I, Pahr S, Resch Y, Roux KH, Srinivasan B, Stentzel S, Vrtala S, Willison LAN, Wickman M, Lødrup-Carlsen KC, Antó JM, Bousquet J, Bachert C, Ebner D, Schlederer T, Harwanegg C, Valenta R (2014) Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip. Methods 66:106–119.  https://doi.org/10.1016/j.ymeth.2013.10.008 CrossRefPubMedGoogle Scholar
  126. 126.
    Lupinek C, Wollmann E, Valenta R (2016) Monitoring allergen immunotherapy effects by microarray. Curr Treat Options Allergy 3:189–203.  https://doi.org/10.1007/s40521-016-0084-2 CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Shamji MH, Wilcock LK, Wachholz PA, Dearman RJ, Kimber I, Wurtzen PA, Larche M, Durham SR, Francis JN (2006) The IgE-facilitated allergen binding (FAB) assay: validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses. J Immunol Methods 317:71–79.  https://doi.org/10.1016/j.jim.2006.09.004 CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O (2005) Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol 116:608–613.  https://doi.org/10.1016/j.jaci.2005.06.004 CrossRefPubMedGoogle Scholar
  129. 129.
    Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, Valenta R, Niederberger V (2005) Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol 116:347–354.  https://doi.org/10.1016/j.jaci.2005.04.003 CrossRefPubMedGoogle Scholar
  130. 130.
    Gehlhar K, Schlaak M, Becker W, Bufe A (1999) Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome. Clin Exp Allergy 29:497–506CrossRefGoogle Scholar
  131. 131.
    Moverare R, Elfman L, Vesterinen E, Metso T, Haahtela T (2002) Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and Pharmacia CAP system. Allergy 57:423–430CrossRefGoogle Scholar
  132. 132.
    Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI (2011) Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in north American adults. J Allergy Clin Immunol 127:72-80, 80.e71-72.  https://doi.org/10.1016/j.jaci.2010.11.035 CrossRefGoogle Scholar
  133. 133.
    Shamji MH, Ljorring C, Francis JN, Calderon MA, Larche M, Kimber I, Frew AJ, Ipsen H, Lund K, Wurtzen PA, Durham SR (2012) Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy 67:217–226.  https://doi.org/10.1111/j.1398-9995.2011.02745.x CrossRefPubMedGoogle Scholar
  134. 134.
    James LK, Shamji MH, Walker SM, Wilson DR, Wachholz PA, Francis JN, Jacobson MR, Kimber I, Till SJ, Durham SR (2011) Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies. J Allergy Clin Immunol 127:509-516.e501-505.  https://doi.org/10.1016/j.jaci.2010.12.1080 Google Scholar
  135. 135.
    Lichtenstein LM, Norman PS, Winkenwerder WL (1968) Antibody response following immunotherapy in ragweed hay fever: Allpyral vs. whole ragweed extract. J Allergy 41:49–57CrossRefGoogle Scholar
  136. 136.
    Platts-Mills TA, von Maur RK, Ishizaka K, Norman PS, Lichtenstein LM (1976) IgA and IgG anti-ragweed antibodies in nasal secretions. Quantitative measurements of antibodies and correlation with inhibition of histamine release. J Clin Invest 57:1041–1050.  https://doi.org/10.1172/jci108346 CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Durham SR, Emminger W, Kapp A, de Monchy JG, Rak S, Scadding GK, Wurtzen PA, Andersen JS, Tholstrup B, Riis B, Dahl R (2012) SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol 129:717-725.e715.  https://doi.org/10.1016/j.jaci.2011.12.973 CrossRefGoogle Scholar
  138. 138.
    Petersen AB, Gudmann P, Milvang-Gronager P, Morkeberg R, Bogestrand S, Linneberg A, Johansen N (2004) Performance evaluation of a specific IgE assay developed for the ADVIA centaur immunoassay system. Clin Biochem 37:882–892.  https://doi.org/10.1016/j.clinbiochem.2004.06.010 CrossRefPubMedGoogle Scholar
  139. 139.
    Razafindratsita A, Saint-Lu N, Mascarell L, Berjont N, Bardon T, Betbeder D, Van Overtvelt L, Moingeon P (2007) Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation. J Allergy Clin Immunol 120:278–285.  https://doi.org/10.1016/j.jaci.2007.04.009 CrossRefPubMedGoogle Scholar
  140. 140.
    Konstantinou GN, Nowak-Wegrzyn A, Bencharitiwong R, Bardina L, Sicherer SH, Sampson HA (2014) Egg-white-specific IgA and IgA2 antibodies in egg-allergic children: is there a role in tolerance induction? Pediatr Allergy Immunol 25:64–70.  https://doi.org/10.1111/pai.12143 CrossRefPubMedGoogle Scholar
  141. 141.
    Wollmann E, Lupinek C, Kundi M, Selb R, Niederberger V, Valenta R (2015) Reduction in allergen-specific IgE binding as measured by microarray: a possible surrogate marker for effects of specific immunotherapy. J Allergy Clin Immunol 136:806-809.e807.  https://doi.org/10.1016/j.jaci.2015.02.034 CrossRefGoogle Scholar
  142. 142.
    Pulendran B, Tang H, Manicassamy S (2010) Programming dendritic cells to induce T(H)2 and tolerogenic responses. Nat Immunol 11:647–655.  https://doi.org/10.1038/ni.1894 CrossRefPubMedGoogle Scholar
  143. 143.
    Zimmer A, Bouley J, Le Mignon M et al (2012) A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy. J Allergy Clin Immunol 129:1020–1030.  https://doi.org/10.1016/j.jaci.2012.02.014 CrossRefPubMedGoogle Scholar
  144. 144.
    Gueguen C, Bouley J, Moussu H, Luce S, Duchateau M, Chamot-Rooke J, Pallardy M, Lombardi V, Nony E, Baron-Bodo V, Mascarell L, Moingeon P (2016) Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy. J Allergy Clin Immunol 137:545–558.  https://doi.org/10.1016/j.jaci.2015.09.015 CrossRefPubMedGoogle Scholar
  145. 145.
    Ruiter B, Shreffler WG (2012) The role of dendritic cells in food allergy. J Allergy Clin Immunol 129:921–928.  https://doi.org/10.1016/j.jaci.2012.01.080 CrossRefPubMedGoogle Scholar
  146. 146.
    Bunning BJ, DeKruyff RH, Nadeau KC (2016) Epigenetic changes during food-specific immunotherapy. Curr Allergy Asthma Rep 16:87.  https://doi.org/10.1007/s11882-016-0665-y CrossRefPubMedGoogle Scholar
  147. 147.
    Hong X, Ladd-Acosta C, Hao K et al. (2016) Epigenome-wide association study links site-specific DNA methylation changes with cow’s milk allergy. J Allergy Clin Immunol 138:908-911.e909.  https://doi.org/10.1016/j.jaci.2016.01.056 CrossRefGoogle Scholar
  148. 148.
    Berni Canani R, Paparo L, Nocerino R, Cosenza L, Pezzella V, Di Costanzo M, Capasso M, Del Monaco V, D'Argenio V, Greco L, Salvatore F (2015) Differences in DNA methylation profile of Th1 and Th2 cytokine genes are associated with tolerance acquisition in children with IgE-mediated cow’s milk allergy. Clin Epigenetics 7:38.  https://doi.org/10.1186/s13148-015-0070-8 CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Swamy RS, Reshamwala N, Hunter T, Vissamsetti S, Santos CB, Baroody FM, Hwang PH, Hoyte EG, Garcia MA, Nadeau KC (2012) Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immunol 130:215-224.e217.  https://doi.org/10.1016/j.jaci.2012.04.021 CrossRefGoogle Scholar
  150. 150.
    Martino D, Dang T, Sexton-Oates A, Prescott S, Tang ML, Dharmage S, Gurrin L, Koplin J, Ponsonby AL, Allen KJ, Saffery R (2015) Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants. J Allergy Clin Immunol 135:1319-1328.e1311-1312.  https://doi.org/10.1016/j.jaci.2014.12.1933 CrossRefGoogle Scholar

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

Authors and Affiliations

  1. 1.Sean N. Parker Center for Allergy and Asthma Research at Stanford UniversityStanford UniversityStanfordUSA
  2. 2.Division of Pulmonary and Critical Care MedicineStanford UniversityStanfordUSA
  3. 3.Division of Allergy, Immunology and Rheumatology, Department of MedicineStanford UniversityStanfordUSA
  4. 4.Department of MedicineStanford University School of MedicineStanfordUSA

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