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Published in: Current Allergy and Asthma Reports 6/2015

01-06-2015 | Immunotherapy and Immunomodulators (B Vickery, Section Editor)

An Examination of Clinical and Immunologic Outcomes in Food Allergen Immunotherapy by Route of Administration

Authors: David Chiang, M. Cecilia Berin

Published in: Current Allergy and Asthma Reports | Issue 6/2015

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Abstract

Allergen immunotherapy for the treatment of food allergy has been a subject of intensive study within the last 10 years. After an unsuccessful attempt with subcutaneous immunotherapy for peanut allergy, other routes with varying degrees of safety and efficacy have been tested for peanut, milk, and egg allergies. In this review, we summarize the results to date with oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy for the treatment of food allergy. While results of immunotherapy trials are promising, increases in efficacy are commonly associated with an increased side effect profile. There is a need for additional research beginning at the preclinical level to develop safe and effective treatments for food allergy.
Literature
3.
go back to reference Nelson HS, Lahr J, Rule R, Bock A, Leung D. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol. 1997;99(6 Pt 1):744–51.PubMedCrossRef Nelson HS, Lahr J, Rule R, Bock A, Leung D. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol. 1997;99(6 Pt 1):744–51.PubMedCrossRef
4.
go back to reference Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY. Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol. 1992;90(2):256–62.PubMedCrossRef Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY. Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol. 1992;90(2):256–62.PubMedCrossRef
7.
go back to reference Patriarca G, Schiavino D, Nucera E, Schinco G, Milani A, Gasbarrini GB. Food allergy in children: results of a standardized protocol for oral desensitization. Hepato-Gastroenterology. 1998;45(19):52–8.PubMed Patriarca G, Schiavino D, Nucera E, Schinco G, Milani A, Gasbarrini GB. Food allergy in children: results of a standardized protocol for oral desensitization. Hepato-Gastroenterology. 1998;45(19):52–8.PubMed
8.•
go back to reference Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, Gorelik M, Schroeder J, Hamilton RG, et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol. 2014. doi:10.1016/j.jaci.2014.11.005. A direct comparison of the efficacy of SLIT and OIT for the treatment of peanut allergy. Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, Gorelik M, Schroeder J, Hamilton RG, et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol. 2014. doi:10.​1016/​j.​jaci.​2014.​11.​005. A direct comparison of the efficacy of SLIT and OIT for the treatment of peanut allergy.
10.•
go back to reference Vickery BP, Scurlock AM, Kulis M, Steele PH, Kamilaris J, Berglund JP, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol. 2014;133(2):468–75. doi:10.1016/j.jaci.2013.11.007. A long-term follow up of subjects receiving peanut OIT up to five years, with assessment of maintenance of tolerance to peanut after discontinuation of OIT.PubMedCentralPubMedCrossRef Vickery BP, Scurlock AM, Kulis M, Steele PH, Kamilaris J, Berglund JP, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol. 2014;133(2):468–75. doi:10.​1016/​j.​jaci.​2013.​11.​007. A long-term follow up of subjects receiving peanut OIT up to five years, with assessment of maintenance of tolerance to peanut after discontinuation of OIT.PubMedCentralPubMedCrossRef
13.••
go back to reference Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367(3):233–43. doi:10.1056/NEJMoa1200435. A landmark multi-center double-blind randomized placebo-controlled study of OIT for egg that assessed outcomes including both desensitization and sustained unresponsiveness.PubMedCentralPubMedCrossRef Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367(3):233–43. doi:10.​1056/​NEJMoa1200435. A landmark multi-center double-blind randomized placebo-controlled study of OIT for egg that assessed outcomes including both desensitization and sustained unresponsiveness.PubMedCentralPubMedCrossRef
15.•
go back to reference Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2012;129(2):448–55. doi:10.1016/j.jaci.2011.10.023. 55 e1–5. A direct comparison of SLIT and two doses of OIT for the treatment of milk allergy, showing a dose effect on the induction of desensitization and sustained unresponsiveness.PubMedCentralPubMedCrossRef Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2012;129(2):448–55. doi:10.​1016/​j.​jaci.​2011.​10.​023. 55 e1–5. A direct comparison of SLIT and two doses of OIT for the treatment of milk allergy, showing a dose effect on the induction of desensitization and sustained unresponsiveness.PubMedCentralPubMedCrossRef
17.•
go back to reference Caminiti L, Pajno GB, Crisafulli G, Chiera F, Collura M, Panasci G, et al. Oral immunotherapy for egg allergy: a double-blind placebo-controlled study, with postdesensitization follow-up. J Allergy Clin Immunol Pract. 2015. doi:10.1016/j.jaip.2015.01.017. A double-blind placebo-controlled study of egg OIT, followed by inclusion of egg into the diet and a sustained unresponsiveness challenge.PubMed Caminiti L, Pajno GB, Crisafulli G, Chiera F, Collura M, Panasci G, et al. Oral immunotherapy for egg allergy: a double-blind placebo-controlled study, with postdesensitization follow-up. J Allergy Clin Immunol Pract. 2015. doi:10.​1016/​j.​jaip.​2015.​01.​017. A double-blind placebo-controlled study of egg OIT, followed by inclusion of egg into the diet and a sustained unresponsiveness challenge.PubMed
18.
go back to reference Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol. 2008;122(6):1154–60. doi:10.1016/j.jaci.2008.09.030. Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol. 2008;122(6):1154–60. doi:10.​1016/​j.​jaci.​2008.​09.​030.
20.
go back to reference Vazquez-Ortiz M, Alvaro-Lozano M, Alsina L, Garcia-Paba MB, Piquer-Gibert M, Giner-Munoz MT, et al. Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2013;43(1):92–102. doi:10.1111/cea.12012.CrossRef Vazquez-Ortiz M, Alvaro-Lozano M, Alsina L, Garcia-Paba MB, Piquer-Gibert M, Giner-Munoz MT, et al. Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2013;43(1):92–102. doi:10.​1111/​cea.​12012.CrossRef
21.
go back to reference Vazquez-Ortiz M, Alvaro M, Piquer M, Dominguez O, Machinena A, Martin-Mateos MA, et al. Baseline specific IgE levels are useful to predict safety of oral immunotherapy in egg-allergic children. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2014;44(1):130–41. doi:10.1111/cea.12233.CrossRef Vazquez-Ortiz M, Alvaro M, Piquer M, Dominguez O, Machinena A, Martin-Mateos MA, et al. Baseline specific IgE levels are useful to predict safety of oral immunotherapy in egg-allergic children. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2014;44(1):130–41. doi:10.​1111/​cea.​12233.CrossRef
22.
go back to reference Morais Silva P, Antunes J, Chambel M, Prates S, Leiria PP. Diagnosis of eosinophilic esophagitis in an infant undergoing milk oral immunotherapy—a case report. Eur Ann Allergy Clin Immunol. 2014;46(4):154–6.PubMed Morais Silva P, Antunes J, Chambel M, Prates S, Leiria PP. Diagnosis of eosinophilic esophagitis in an infant undergoing milk oral immunotherapy—a case report. Eur Ann Allergy Clin Immunol. 2014;46(4):154–6.PubMed
23.
go back to reference Ridolo E, De Angelis GL, Dall’aglio P. Eosinophilic esophagitis after specific oral tolerance induction for egg protein. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2011;106(1):73–4. doi:10.1016/j.anai.2010.10.010.CrossRef Ridolo E, De Angelis GL, Dall’aglio P. Eosinophilic esophagitis after specific oral tolerance induction for egg protein. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2011;106(1):73–4. doi:10.​1016/​j.​anai.​2010.​10.​010.CrossRef
25.
go back to reference Fuentes-Aparicio V, Alvarez-Perea A, Infante S, Zapatero L, D’Oleo A, Alonso-Lebrero E. Specific oral tolerance induction in paediatric patients with persistent egg allergy. Allergol Immunopathol. 2013;41(3):143–50. doi:10.1016/j.aller.2012.02.007.CrossRef Fuentes-Aparicio V, Alvarez-Perea A, Infante S, Zapatero L, D’Oleo A, Alonso-Lebrero E. Specific oral tolerance induction in paediatric patients with persistent egg allergy. Allergol Immunopathol. 2013;41(3):143–50. doi:10.​1016/​j.​aller.​2012.​02.​007.CrossRef
27.
go back to reference Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2014;113(6):624–9. doi:10.1016/j.anai.2014.08.004.CrossRef Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2014;113(6):624–9. doi:10.​1016/​j.​anai.​2014.​08.​004.CrossRef
28.•
go back to reference Keet CA, Seopaul S, Knorr S, Narisety S, Skripak J, Wood RA. Long-term follow-up of oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol. 2013;132(3):737–9 e6. doi:10.1016/j.jaci.2013.05.006. This long-term follow-up of a milk OIT study provides data showing that successful completion of a sustained unresponsiveness challenge does not necessarily predict successful incorporation of milk into the diet, and highlights the need for long-term study of food immunotherapy outcomes.PubMedCentralPubMedCrossRef Keet CA, Seopaul S, Knorr S, Narisety S, Skripak J, Wood RA. Long-term follow-up of oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol. 2013;132(3):737–9 e6. doi:10.​1016/​j.​jaci.​2013.​05.​006. This long-term follow-up of a milk OIT study provides data showing that successful completion of a sustained unresponsiveness challenge does not necessarily predict successful incorporation of milk into the diet, and highlights the need for long-term study of food immunotherapy outcomes.PubMedCentralPubMedCrossRef
34.
go back to reference Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Benhamou PH, et al. Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice. J Immunol. 2011;186(10):5629–37. doi:10.4049/jimmunol.1003134.PubMedCrossRef Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Benhamou PH, et al. Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice. J Immunol. 2011;186(10):5629–37. doi:10.​4049/​jimmunol.​1003134.PubMedCrossRef
38.•
go back to reference Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, et al. The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2014;44(6):867–81. doi:10.1111/cea.12312. This pre-clinical study shows that application of allergen by the epicutaneous route can generate regulatory tolerance and suppress allergic inflammation in the gastrointestinal tract.CrossRef Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, et al. The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2014;44(6):867–81. doi:10.​1111/​cea.​12312. This pre-clinical study shows that application of allergen by the epicutaneous route can generate regulatory tolerance and suppress allergic inflammation in the gastrointestinal tract.CrossRef
39.
go back to reference Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH. Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol. 2010;125(5):1165–7. doi:10.1016/j.jaci.2010.02.029.PubMedCrossRef Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH. Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol. 2010;125(5):1165–7. doi:10.​1016/​j.​jaci.​2010.​02.​029.PubMedCrossRef
40.
go back to reference Dupont C, Bourrier T, de Blay F, Guénard-Bilbault L, Sauvage C, Cousin M-O, et al. Peanut epicutaneous immunotherapy (EPIT) in peanut-allergic children: 18 months treatment in the Arachild Study. J Allergy Clin Immunol. 2014;133(2, Supplement):AB102. doi:10.1016/j.jaci.2013.12.381.CrossRef Dupont C, Bourrier T, de Blay F, Guénard-Bilbault L, Sauvage C, Cousin M-O, et al. Peanut epicutaneous immunotherapy (EPIT) in peanut-allergic children: 18 months treatment in the Arachild Study. J Allergy Clin Immunol. 2014;133(2, Supplement):AB102. doi:10.​1016/​j.​jaci.​2013.​12.​381.CrossRef
41.
go back to reference Sampson HA, Agbotounou W, Thébault C, Charles R, Martin L, Yang WH, et al. Epicutaneous immunotherapy (EPIT) is effective and safe to treat peanut allergy: a multi-national double-blind placebo-controlled randomized phase IIb trial. J Allergy Clin Immunol. 2015;135(2, Supplement):AB390. doi:10.1016/j.jaci.2014.12.1901.CrossRef Sampson HA, Agbotounou W, Thébault C, Charles R, Martin L, Yang WH, et al. Epicutaneous immunotherapy (EPIT) is effective and safe to treat peanut allergy: a multi-national double-blind placebo-controlled randomized phase IIb trial. J Allergy Clin Immunol. 2015;135(2, Supplement):AB390. doi:10.​1016/​j.​jaci.​2014.​12.​1901.CrossRef
42.•
go back to reference Syed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133(2):500–10. doi:10.1016/j.jaci.2013.12.1037. This mechanistic study identifies a key role of dendritic cells in determining the regulatory phenotype of T cells after OIT.PubMedCentralPubMedCrossRef Syed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133(2):500–10. doi:10.​1016/​j.​jaci.​2013.​12.​1037. This mechanistic study identifies a key role of dendritic cells in determining the regulatory phenotype of T cells after OIT.PubMedCentralPubMedCrossRef
43.•
go back to reference Gorelik M, Narisety SD, Guerrerio AL, Chichester KL, Keet CA, Bieneman AP, et al. Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol. 2014. doi:10.1016/j.jaci.2014.11.010. This mechanistic study shows that immune modifications induced by OIT and SLIT are not sustained, potentially explaining the need for maintained allergen exposure. Bystander effects of immunotherapy on basophil and T cell responses to dust mite are shown. Gorelik M, Narisety SD, Guerrerio AL, Chichester KL, Keet CA, Bieneman AP, et al. Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol. 2014. doi:10.​1016/​j.​jaci.​2014.​11.​010. This mechanistic study shows that immune modifications induced by OIT and SLIT are not sustained, potentially explaining the need for maintained allergen exposure. Bystander effects of immunotherapy on basophil and T cell responses to dust mite are shown.
44.
go back to reference Frischmeyer-Guerrerio PA, Keet CA, Guerrerio AL, Chichester KL, Bieneman AP, Hamilton RG, et al. Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy. Clin Immunol. 2014;155(1):47–59. doi:10.1016/j.clim.2014.08.006.PubMedCrossRef Frischmeyer-Guerrerio PA, Keet CA, Guerrerio AL, Chichester KL, Bieneman AP, Hamilton RG, et al. Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy. Clin Immunol. 2014;155(1):47–59. doi:10.​1016/​j.​clim.​2014.​08.​006.PubMedCrossRef
45.
go back to reference Thyagarajan A, Jones SM, Calatroni A, Pons L, Kulis M, Woo CS, et al. Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2012;42(8):1197–205. doi:10.1111/j.1365-2222.2012.04028.x.CrossRef Thyagarajan A, Jones SM, Calatroni A, Pons L, Kulis M, Woo CS, et al. Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2012;42(8):1197–205. doi:10.​1111/​j.​1365-2222.​2012.​04028.​x.CrossRef
46.
go back to reference Burton OT, Logsdon SL, Zhou JS, Medina-Tamayo J, Abdel-Gadir A, Noval Rivas M, et al. Oral immunotherapy induces IgG antibodies that act through FcgammaRIIb to suppress IgE-mediated hypersensitivity. J Allergy Clin Immunol. 2014;134(6):1310–7 e6. doi:10.1016/j.jaci.2014.05.042.PubMedCrossRef Burton OT, Logsdon SL, Zhou JS, Medina-Tamayo J, Abdel-Gadir A, Noval Rivas M, et al. Oral immunotherapy induces IgG antibodies that act through FcgammaRIIb to suppress IgE-mediated hypersensitivity. J Allergy Clin Immunol. 2014;134(6):1310–7 e6. doi:10.​1016/​j.​jaci.​2014.​05.​042.PubMedCrossRef
47.
go back to reference Bedoret D, Singh AK, Shaw V, Hoyte EG, Hamilton R, DeKruyff RH, et al. Changes in antigen-specific T-cell number and function during oral desensitization in cow’s milk allergy enabled with omalizumab. Mucosal Immunol. 2012;5(3):267–76. doi:10.1038/mi.2012.5.PubMedCentralPubMedCrossRef Bedoret D, Singh AK, Shaw V, Hoyte EG, Hamilton R, DeKruyff RH, et al. Changes in antigen-specific T-cell number and function during oral desensitization in cow’s milk allergy enabled with omalizumab. Mucosal Immunol. 2012;5(3):267–76. doi:10.​1038/​mi.​2012.​5.PubMedCentralPubMedCrossRef
48.
49.
50.
go back to reference Zaleska A, Eiwegger T, Soyer O, van de Veen W, Rhyner C, Soyka MB, et al. Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine. Allergy. 2014;69(9):1162–70. doi:10.1111/all.12461.PubMedCrossRef Zaleska A, Eiwegger T, Soyer O, van de Veen W, Rhyner C, Soyka MB, et al. Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine. Allergy. 2014;69(9):1162–70. doi:10.​1111/​all.​12461.PubMedCrossRef
Metadata
Title
An Examination of Clinical and Immunologic Outcomes in Food Allergen Immunotherapy by Route of Administration
Authors
David Chiang
M. Cecilia Berin
Publication date
01-06-2015
Publisher
Springer US
Published in
Current Allergy and Asthma Reports / Issue 6/2015
Print ISSN: 1529-7322
Electronic ISSN: 1534-6315
DOI
https://doi.org/10.1007/s11882-015-0536-y

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