Skip to main content
SpringerLink
Log in

Comparison of sublingual immunotherapy and oral immunotherapy in peanut allergy

  • mini-review
  • Published:
Allergo Journal International Aims and scope Submit manuscript

Abstract

The prevalence of food allergy has been increasing over the past few decades at an alarming rate with peanut allergy affecting about 2% of children. Both oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) have shown promise as a treatment option for peanut allergy. Immunotherapy induces desensitization and reduces the risk of reaction during accidental ingestion and may also enable those who are successfully desensitized to include the food allergen in their diet. OIT has been very well studied and has been found to be more efficacious than SLIT with an acceptable safety profile. However, SLIT is associated with fewer side effects. Studies indicate that a combination of SLIT and OIT may together induce a significant increase in challenge thresholds with fewer adverse events. More head-to-head clinical trials that directly compare OIT and SLIT as well as SLIT and OIT combination studies are warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AIT:

Allergen-specific immunotherapy

BHR:

Bronchial hyper-responsiveness

Bregs:

B regulatory cells

DBPCFC:

Double-blind placebo-controlled food challenge

FA:

Food allergy

OIT:

Oral immunotherapy

PPOIT:

Probiotic with peanut OIT

SLIT:

Sublingual immunotherapy

SU:

Sustained unresponsiveness

Th:

T-helper

Tregs:

Regulatory T cells

References

  1. Savage J, Johns CB. Food allergy: epidemiology and natural history. Immunol Allergy Clin North Am. 2015;35:45–59.

    Article  PubMed  Google Scholar 

  2. Warren CM, Otto AK, Walkner MM, Gupta RS. Quality of life among food allergic patients and their caregivers. Curr Allergy Asthma Rep. 2016;16:38.

    Article  PubMed  CAS  Google Scholar 

  3. Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128:e9–e17.

    Article  PubMed  Google Scholar 

  4. Peters RL, Koplin JJ, Gurrin LC, Dharmage SC, Wake M, Ponsonby AL, et al. The prevalence of food allergy and other allergic diseases in early childhood in a population-based study: HealthNuts age 4‑year follow-up. J Allergy Clin Immunol. 2017;140:145–153e8..

    Article  PubMed  Google Scholar 

  5. Savage JH, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy. J Allergy Clin Immunol. 2007;120:1413–7.

    Article  PubMed  CAS  Google Scholar 

  6. Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow’s milk allergy. J Allergy Clin Immunol. 2007;120:1172–7.

    Article  PubMed  CAS  Google Scholar 

  7. Begin P, Paradis L, Paradis J, Picard M, Des Roches A. Natural resolution of peanut allergy: a 12-year longitudinal follow-up study. J Allergy Clin Immunol Pract. 2013;1:528–530e1-4.

    Article  PubMed  Google Scholar 

  8. Vander Leek TK, Liu AH, Stefanski K, Blacker B, Bock SA. The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. J Pediatr. 2000;137:749–55.

    Article  PubMed  CAS  Google Scholar 

  9. Kostadinova AI, Willemsen LE, Knippels LM, Garssen J. Immunotherapy—risk/benefit in food allergy. Pediatr Allergy Immunol. 2013;24:633–44.

    Article  PubMed  Google Scholar 

  10. 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;99:744–51.

    Article  PubMed  CAS  Google Scholar 

  11. Sampson HA, Shreffler WG, Yang WH, Sussman GL, Brown-Whitehorn TF, Nadeau KC, et al. Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: a randomized clinical trial. JAMA. 2017;318:1798–809.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Nowak-Wegrzyn A, Fiocchi A. Is oral immunotherapy the cure for food allergies? Curr Opin Allergy Clin Immunol. 2010;10:214–9.

    Article  PubMed  Google Scholar 

  13. Rolinck-Werninghaus C, Staden U, Mehl A, Hamelmann E, Beyer K, Niggemann B. Specific oral tolerance induction with food in children: transient or persistent effect on food allergy? Allergy. 2005;60:1320–2.

    Article  PubMed  CAS  Google Scholar 

  14. Hussey Freeland DM, Fan-Minogue H, Spergel JM, Chatila TA, Nadeau KC. Advances in food allergy oral immunotherapy: toward tolerance. Curr Opin Immunol. 2016;42:119–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Rachid R, Umetsu DT. Immunological mechanisms for desensitization and tolerance in food allergy. Semin Immunopathol. 2012;34:689–702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organ J. 2015;8:17.

    Article  PubMed  CAS  Google Scholar 

  17. Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133:621–31.

    Article  PubMed  CAS  Google Scholar 

  18. Vickery BP, Scurlock AM, Jones SM, Burks AW. Mechanisms of immune tolerance relevant to food allergy. J Allergy Clin Immunol. 2011;127:576–84. quiz 85–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Yu W, Freeland DMH, Nadeau KC. Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol. 2016;16:751–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Jay DC, Nadeau KC. Immune mechanisms of sublingual immunotherapy. Curr Allergy Asthma Rep. 2014;14:473.

    Article  PubMed  CAS  Google Scholar 

  21. Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124:292–300, e1-97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Hofmann AM, Scurlock AM, Jones SM, Palmer KP, Lokhnygina Y, Steele PH, et al. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol. 2009;124:286–91, 91 e1-6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011;127:654–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Anagnostou K, Islam S, King Y, Foley L, Pasea L, Bond S, et al. Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. Lancet. 2014;383:1297–304.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Kukkonen AK, Uotila R, Malmberg LP, Pelkonen AS, Makela MJ. Double-blind placebo-controlled challenge showed that peanut oral immunotherapy was effective for severe allergy without negative effects on airway inflammation. Acta Paediatr. 2017;106:274–81.

    Article  PubMed  CAS  Google Scholar 

  26. 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;133:468–75.

    Article  PubMed  CAS  Google Scholar 

  27. Vickery BP, Berglund JP, Burk CM, Fine JP, Kim EH, Kim JI, et al. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. J Allergy Clin Immunol. 2017;139:173–181e8.

    Article  PubMed  CAS  Google Scholar 

  28. Nagakura KI, Sato S, Yanagida N, Nishino M, Asaumi T, Ogura K, et al. Oral immunotherapy in Japanese children with anaphylactic peanut allergy. Int Arch Allergy Immunol. 2018;175:181–8.

    Article  PubMed  CAS  Google Scholar 

  29. Bird JA, Spergel JM, Jones SM, Rachid R, Assa’ad AH, Wang J, et al. Efficacy and safety of AR101 in oral immunotherapy for peanut allergy: results of ARC001, a randomized, double-blind, placebo-controlled phase 2 clinical trial. J Allergy Clin Immunol Pract. 2018;6:476–485.e3.

    Article  PubMed  Google Scholar 

  30. Tang ML, Ponsonby AL, Orsini F, Tey D, Robinson M, Su EL, et al. Administration of a probiotic with peanut oral immunotherapy: A randomized trial. J Allergy Clin Immunol. 2015;135:737–744e8.

    Article  PubMed  CAS  Google Scholar 

  31. Hsiao K‑C, Ponsonby A‑L, Axelrad C, Pitkin S, Tang MLK, Burks W, et al. Long-term clinical and immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4‑year follow-up of a randomised, double-blind, placebo-controlled trial. Lancet Child Adolesc Health. 2017;1:97–105.

    Article  PubMed  Google Scholar 

  32. Dantzer JA, Wood RA. The use of omalizumab in allergen immunotherapy. Clin Exp Allergy. 2018;48:232–40.

    Article  PubMed  CAS  Google Scholar 

  33. Schneider LC, Rachid R, LeBovidge J, Blood E, Mittal M, Umetsu DT. A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol. 2013;132:1368–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. MacGinnitie AJ, Rachid R, Gragg H, Little SV, Lakin P, Cianferoni A, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. J Allergy Clin Immunol. 2017;139:873–881e8.

    Article  PubMed  CAS  Google Scholar 

  35. 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;129:448–455, 55 e1-5.

    Article  PubMed  CAS  Google Scholar 

  36. Mempel M, Rakoski J, Ring J, Ollert M. Severe anaphylaxis to kiwi fruit: Immunologic changes related to successful sublingual allergen immunotherapy. J Allergy Clin Immunol. 2003;111:1406–9.

    Article  PubMed  Google Scholar 

  37. Kim EH, Bird JA, Kulis M, Laubach S, Pons L, Shreffler W, et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J Allergy Clin Immunol. 2011;127:640–646e1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Fleischer DM, Burks AW, Vickery BP, Scurlock AM, Wood RA, Jones SM, et al. Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial. J Allergy Clin Immunol. 2013;131:119–127e1-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Burks AW, Wood RA, Jones SM, Sicherer SH, Fleischer DM, Scurlock AM, et al. Sublingual immunotherapy for peanut allergy: long-term follow-up of a randomized multicenter trial. J Allergy Clin Immunol. 2015;135:1240–1248.e1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. 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. 2015;135:1275–1282e6.

    Article  PubMed  CAS  Google Scholar 

  41. Andorf S, Purington N, Block WM, Long AJ, Tupa D, Brittain E, et al. Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial. Lancet Gastroenterol Hepatol. 2018;3:85–94.

    Article  PubMed  Google Scholar 

  42. Blumchen K, Ulbricht H, Staden U, Dobberstein K, Beschorner J, de Oliveira LC, et al. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol. 2010;126:83–91e1.

    Article  PubMed  CAS  Google Scholar 

  43. Anagnostou K, Clark A, King Y, Islam S, Deighton J, Ewan P. Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome. Clin Exp Allergy. 2011;41:1273–81.

    Article  PubMed  CAS  Google Scholar 

  44. Chin SJ, Vickery BP, Kulis MD, Kim EH, Varshney P, Steele P, et al. Sublingual versus oral immunotherapy for peanut-allergic children: a retrospective comparison. J Allergy Clin Immunol. 2013;132:476–478e2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

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.

Author information

Authors and Affiliations

  1. Sean N. Parker Center for Allergy and Asthma Research, Stanford University, 94305, Stanford, CA, USA

    Wenming Zhang PhD, Sayantani B. Sindher MD, Vanitha Sampath PhD & Kari Nadeau MD, PhD

  2. Division of Pulmonary and Critical Care Medicine, Stanford University, 94305, Stanford, CA, USA

    Wenming Zhang PhD, Sayantani B. Sindher MD, Vanitha Sampath PhD & Kari Nadeau MD, PhD

  3. Division of Allergy, Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA

    Kari Nadeau MD, PhD

Authors
  1. Wenming Zhang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sayantani B. Sindher MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vanitha Sampath PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kari Nadeau MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kari Nadeau MD, PhD.

Ethics declarations

Conflict of interest

W. Zhang, S.B. Sindher, V. Sampath and K. Nadeau declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, W., Sindher, S.B., Sampath, V. et al. Comparison of sublingual immunotherapy and oral immunotherapy in peanut allergy. Allergo J Int 27, 153–161 (2018). https://doi.org/10.1007/s40629-018-0067-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40629-018-0067-x

Keywords

Search

Navigation