Advertisement

New Developments in Non-allergen-specific Therapy for the Treatment of Food Allergy

  • Andrew Long
  • Matteo Borro
  • Vanitha Sampath
  • R. Sharon ChinthrajahEmail author
Food Allergy (E Kim, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Food Allergy

Abstract

Purpose of Review

The prevalence of food allergy is increasing. At the current time, there are no approved treatments for food allergy. Major limitations of immunotherapy are long treatment periods (months or years), frequent clinic visits, high costs, increased risk of adverse events during treatment, and lack of durability of desensitization. Additionally, it is allergen-specific, and in those allergic to multiple allergens, the length and cost of treatment are further increased. In this review, we summarize recent developments in novel non-allergen-specific treatments for food allergy.

Recent Findings

A number of monoclonal antibodies that block IgE or specific pro-allergenic cytokines or their receptors have shown promise in clinical trials for food allergy.

Summary

The insight we have gained through the use of one drug for the treatment of an atopic disease is quickly being translated to other atopic diseases, including food allergy. The future for food allergy treatment with biologics looks bright.

Keywords

Food allergy Immunotherapy Biologics Atopy Omalizumab Dupilumab 

Notes

Acknowledgments

We thank Dr. Kari Nadeau for her critical review of the paper.

Author Contributions

AJL, MB, and VS performed the literature search and drafted and critically revised the work. RSC drafted and critically reviewed the work.

Funding Information

This work was financially supported by the Sean N. Parker Center for Allergy and Asthma Research at Stanford University.

Compliance with Ethical Standards

Conflict of Interest

Dr. Sharon Chinthrajah receives grant support from CoFAR NIAID, Aimmune, DBV Technologies, Astellas, AnaptysBio, Novartis, and Regeneron and is a scientific advisory board member for Alladapt Immunotherapeutics. All other authors declare no conflict of interest.

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.

References

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

  1. 1.
    Gupta RS, Warren CM, Smith BM, Blumenstock JA, Jiang J, Davis MM, et al. The public health impact of parent-reported childhood food allergies in the United States. Pediatrics. 2018;142.Google Scholar
  2. 2.
    Gupta RS, Warren CM, Smith BM, Jiang J, Blumenstock JA, Davis MM, et al. Prevalence and severity of food allergies among US adults. JAMA Netw Open. 2019;2:e185630.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Robbins KA, Uygungil B. Nutritional deficiencies and food allergy. J Allergy Clin Immunol Pract. 2017;5:528–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Meyer R. Nutritional disorders resulting from food allergy in children. Pediatr Allergy Immunol. 2018;29:689–704.PubMedCrossRefGoogle Scholar
  5. 5.
    Greenhawt M. Food allergy quality of life and living with food allergy. Curr Opin Allergy Clin Immunol. 2016;16:284–90.PubMedCrossRefGoogle Scholar
  6. 6.
    Nwaru BI, Hickstein L, Panesar SS, Roberts G, Muraro A, Sheikh A, et al. Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy. 2014;69:992–1007.PubMedCrossRefGoogle Scholar
  7. 7.
    Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014;69:1008–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Sicherer SH, Sampson HA. Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol. 2018;141:41–58.PubMedCrossRefGoogle Scholar
  9. 9.
    Davis CM, Kelso JM. Food allergy management. Immunol Allergy Clin N Am. 2018;38:53–64.CrossRefGoogle Scholar
  10. 10.
    Luyt D, Ball H, Kirk K, Stiefel G. Diagnosis and management of food allergy in children. Paediatr Child Health. 2016;26:287–91.CrossRefGoogle Scholar
  11. 11.
    Motosue MS, Bellolio MF, Van Houten HK, Shah ND, Campbell RL. National trends in emergency department visits and hospitalizations for food-induced anaphylaxis in US children. Pediatr Allergy Immunol. 2018;29:538–44.PubMedCrossRefGoogle Scholar
  12. 12.
    Schofield A. A case of egg poisoning. Lancet. 1908;1:716.CrossRefGoogle Scholar
  13. 13.
    Gernez Y, Nowak-Wegrzyn A. Immunotherapy for food allergy: are we there yet? J Allergy Clin Immunol Pract. 2017;5:250–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Fleischer DM, Greenhawt M, Sussman G, Begin P, Nowak-Wegrzyn A, Petroni D, et al. Effect of epicutaneous immunotherapy vs placebo on reaction to peanut protein ingestion among children with peanut allergy: the PEPITES randomized clinical trial. JAMA. 2019;321:946–55.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Nurmatov U, Dhami S, Arasi S, Pajno GB, Fernandez-Rivas M, Muraro A, et al. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis. Allergy. 2017;72:1133–47.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Chiang D, Berin MC. An examination of clinical and immunologic outcomes in food allergen immunotherapy by route of administration. Curr Allergy Asthma Rep. 2015;15:35.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Wood RA. Food allergen immunotherapy: current status and prospects for the future. J Allergy Clin Immunol. 2016;137:973–82.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Freeland DMH, Manohar M, Andorf S, Hobson BD, Zhang W, Nadeau KC. Oral immunotherapy for food allergy. Semin Immunol. 2017;30:36–44.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Wood RA. Oral immunotherapy for food allergy. J Investig Allergol Clin Immunol. 2017;27:151–9.PubMedCrossRefGoogle Scholar
  21. 21.
    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;367:233–43.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    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;133:500–10.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    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;126:83–91 e1.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    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;129:448–55 55 e1–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Jones SM, Burks AW, Keet C, Vickery BP, Scurlock AM, Wood RA, et al. Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy. J Allergy Clin Immunol. 2016;137:1117–27 e10.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    •• Chinthrajah RS, Purington N, Andorf S, Long A, O’Laughlin KL, Lyu SC, et al. Sustained outcomes in a large double-1 blind, placebo-controlled, randomized phase 2 study of peanut immunotherapy. Lancet. Accepted June 14,2019 In Press. 2019. OIT could desensitize individuals with peanut allergy to 4000 mg peanut protein but discontinuation, or even reduction to 300 mg daily, could increase the likelihood of regaining clinical reactivity to peanut.Google Scholar
  28. 28.
    Duca B, Patel N, Turner PJ. GRADE-ing the benefit/risk equation in food immunotherapy. Curr Allergy Asthma Rep. 2019;19:30.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Scurlock AM. Oral and sublingual immunotherapy for treatment of IgE-mediated food allergy. Clin Rev Allergy Immunol. 2018;55:139–52.PubMedCrossRefGoogle Scholar
  30. 30.
    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. 2014;113:624–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Wright BL, Fernandez-Becker NQ, Kambham N, Purington N, Tupa D, Zhang W, et al. Baseline gastrointestinal eosinophilia is common in oral immunotherapy subjects with IgE-mediated peanut allergy. Front Immunol. 2018;9:2624.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Chu DK, Wood RA, French S, Fiocchi A, Jordana M, Waserman S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. Lancet. 2019.Google Scholar
  33. 33.
    Yu W, Freeland DMH, Nadeau KC. Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol. 2016;16:751–65.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Chinthrajah RS, Hernandez JD, Boyd SD, Galli SJ, Nadeau KC. Molecular and cellular mechanisms of food allergy and food tolerance. J Allergy Clin Immunol. 2016;137:984–97.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Lozano-Ojalvo D, Berin C, Tordesillas L. Immune basis of allergic reactions to food. J Investig Allergol Clin Immunol. 2019;29:1–14.PubMedCrossRefGoogle Scholar
  36. 36.
    Brotons-Canto A, Martin-Arbella N, Gamazo C, Irache JM. New pharmaceutical approaches for the treatment of food allergies. Expert Opin Drug Deliv. 2018;15:675–86.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Aguilera-Insunza R, Venegas LF, Iruretagoyena M, Rojas L, Borzutzky A. Role of dendritic cells in peanut allergy. Expert Rev Clin Immunol. 2018;14:367–78.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Walker MT, Green JE, Ferrie RP, Queener AM, Kaplan MH, Cook-Mills JM. Mechanism for initiation of food allergy: dependence on skin barrier mutations and environmental allergen costimulation. J Allergy Clin Immunol. 2018;141:1711–25 e9.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Tordesillas L, Goswami R, Benede S, Grishina G, Dunkin D, Jarvinen KM, et al. Skin exposure promotes a Th2-dependent sensitization to peanut allergens. J Clin Invest. 2014;124:4965–75.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Divekar R, Kita H. Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation. Curr Opin Allergy Clin Immunol. 2015;15:98–103.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Lee JB, Chen CY, Liu B, Mugge L, Angkasekwinai P, Facchinetti V, et al. IL-25 and CD4(+) TH2 cells enhance type 2 innate lymphoid cell-derived IL-13 production, which promotes IgE-mediated experimental food allergy. J Allergy Clin Immunol. 2016;137:1216–25 e5.PubMedCrossRefGoogle Scholar
  42. 42.
    Leyva-Castillo JM, Galand C, Kam C, Burton O, Gurish M, Musser MA, et al. Mechanical skin injury promotes food anaphylaxis by driving intestinal mast cell expansion. Immunity. 2019;50(5):1262–1275.e4.PubMedCrossRefGoogle Scholar
  43. 43.
    Galand C, Leyva-Castillo JM, Yoon J, Han A, Lee MS, McKenzie ANJ, et al. IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells. J Allergy Clin Immunol. 2016;138:1356–66.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Noval Rivas M, Burton OT, Oettgen HC, Chatila T. IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function. J Allergy Clin Immunol. 2016;138:801–11 e9.PubMedCrossRefGoogle Scholar
  45. 45.
    Pasha MA, Patel G, Hopp R, Yang Q. Role of innate lymphoid cells in allergic diseases. Allergy Asthma Proc. 2019;40:138–45.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Noval Rivas M, Burton OT, Wise P, Charbonnier LM, Georgiev P, Oettgen HC, et al. Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity. 2015;42:512–23.PubMedCrossRefGoogle Scholar
  47. 47.
    Silva-Filho JL, Caruso-Neves C, Pinheiro AAS. IL-4: an important cytokine in determining the fate of T cells. Biophys Rev. 2014;6:111–8.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Pattarini L, Trichot C, Bogiatzi S, Grandclaudon M, Meller S, Keuylian Z, et al. TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand. J Exp Med. 2017;214:1529–46.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Frossard CP, Zimmerli SC, Rincon Garriz JM, Eigenmann PA. Food allergy in mice is modulated through the thymic stromal lymphopoietin pathway. Clin Transl Allergy. 2015;6:2.PubMedCrossRefGoogle Scholar
  50. 50.
    Khodoun MV, Tomar S, Tocker JE, Wang YH, Finkelman FD. Prevention of food allergy development and suppression of established food allergy by neutralization of thymic stromal lymphopoietin, IL-25, and IL-33. J Allergy Clin Immunol. 2018;141:171–9 e1.PubMedCrossRefGoogle Scholar
  51. 51.
    Johnston LK, Hsu CL, Krier-Burris RA, Chhiba KD, Chien KB, McKenzie A, et al. IL-33 precedes IL-5 in regulating eosinophil commitment and is required for eosinophil homeostasis. J Immunol. 2016;197:3445–53.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Wright BL, Kulis M, Orgel KA, Burks AW, Dawson P, Henning AK, et al. Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness. Allergy. 2016;71:1552–60.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Sugimoto M, Kamemura N, Nagao M, Irahara M, Kagami S, Fujisawa T, et al. Differential response in allergen-specific IgE, IgGs, and IgA levels for predicting outcome of oral immunotherapy. Pediatr Allergy Immunol. 2016;27:276–82.PubMedCrossRefGoogle Scholar
  54. 54.
    Pellerin L, Jenks JA, Chinthrajah S, Dominguez T, Block W, Zhou X, et al. Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired. J Allergy Clin Immunol. 2018;141:202–13 e8.PubMedCrossRefGoogle Scholar
  55. 55.
    Ryan JF, Hovde R, Glanville J, Lyu SC, Ji X, Gupta S, et al. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets. Proc Natl Acad Sci U S A. 2016;113:E1286–95.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, et al. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity. 2008;29:771–81.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Santos AF, James LK, Bahnson HT, Shamji MH, Couto-Francisco NC, Islam S, et al. IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens. J Allergy Clin Immunol. 2015;135:1249–56.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Burks AW, Sampson HA, Plaut M, Lack G, Akdis CA. Treatment for food allergy. J Allergy Clin Immunol. 2018;141:1–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Fiocchi A, Artesani MC, Riccardi C, Mennini M, Pecora V, Fierro V, et al. Impact of omalizumab on food allergy in patients treated for asthma: a real-life study. J Allergy Clin Immunol Pract. 2019;7:1901–9 e5.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    •• Andorf S, Purington N, Kumar D, Long A, O’Laughlin KL, Sicherer S, et al. A phase 2 randomized controlled multisite study using omalizumab-facilitated rapid desensitization to test continued vs discontinued dosing in multifood allergic individuals. EClinicalMedicine. 2019;7:27–38. Omalizumb with oral immuotherapy shows promise and decreases time to desensitization and simultaneously desensitizes to multiple allergens. PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    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;139:873–81 e8.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Takahashi M, Soejima K, Taniuchi S, Hatano Y, Yamanouchi S, Ishikawa H, et al. Oral immunotherapy combined with omalizumab for high-risk cow’s milk allergy: a randomized controlled trial. Sci Rep. 2017;7:17453.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Lin C, Lee IT, Sampath V, Dinakar C, DeKruyff RH, Schneider LC, et al. Combining anti-IgE with oral immunotherapy. Pediatr Allergy Immunol. 2017;28:619–27.PubMedCrossRefGoogle Scholar
  64. 64.
    Davies AM, Allan EG, Keeble AH, Delgado J, Cossins BP, Mitropoulou AN, et al. Allosteric mechanism of action of the therapeutic anti-IgE antibody omalizumab. J Biol Chem. 2017;292:9975–87.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Dantzer JA, Wood RA. The use of omalizumab in allergen immunotherapy. Clin Exp Allergy. 2018;48:232–40.PubMedCrossRefGoogle Scholar
  66. 66.
    Kamin W, Kopp MV, Erdnuess F, Schauer U, Zielen S, Wahn U. Safety of anti-IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously. Pediatr Allergy Immunol. 2010;21:e160–5.PubMedCrossRefGoogle Scholar
  67. 67.
    Leung DY, Sampson HA, Yunginger JW, Burks AW Jr, Schneider LC, Wortel CH, et al. Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med. 2003;348:986–93.PubMedCrossRefGoogle Scholar
  68. 68.
    Sampson HA, Leung DY, Burks AW, Lack G, Bahna SL, Jones SM, et al. A phase II, randomized, doubleblind, parallelgroup, placebo-controlled oral food challenge trial of Xolair (omalizumab) in peanut allergy. J Allergy Clin Immunol. 2011;127:1309–10 e1.PubMedCrossRefGoogle Scholar
  69. 69.
    •• Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, et al. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow’s milk allergy. J Allergy Clin Immunol. 2016;137:1103–10 e11. Measurements of safety significantly improved with adjunctive omalizumab in combination with food oral immunotherapy. PubMedGoogle Scholar
  70. 70.
    Begin P, Dominguez T, Wilson SP, Bacal L, Mehrotra A, Kausch B, et al. Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using omalizumab. Allergy, Asthma Clin Immunol. 2014;10:7.CrossRefGoogle Scholar
  71. 71.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT. Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy. J Allergy Clin Immunol. 2011;127:1622–4.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    •• 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. In patients with allergies to multiple foods, omalizumab improves the efficacy of multifood oral immunotherapy and enables safe and rapid desensitisation. CrossRefGoogle Scholar
  74. 74.
    Srivastava KD, Song Y, Yang N, Liu C, Goldberg IE, Nowak-Wegrzyn A, et al. B-FAHF-2 plus oral immunotherapy (OIT) is safer and more effective than OIT alone in a murine model of concurrent peanut/tree nut allergy. Clin Exp Allergy. 2017;47:1038–49.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Patil SP, Wang J, Song Y, Noone S, Yang N, Wallenstein S, et al. Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: extended phase I study. J Allergy Clin Immunol. 2011;128:1259–65 e2.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Wang J, Jones SM, Pongracic JA, Song Y, Yang N, Sicherer SH, et al. Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy. J Allergy Clin Immunol. 2015;136:962–70 e1.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    •• Frischmeyer-Guerrerio PA, Masilamani M, Gu W, Brittain E, Wood R, Kim J, et al. Mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2017;140:1043–53 e8. Baseline biomarkers (alterations in basophil reactivity) can identify subjects most likely to benefit from adjunctive therapy with omalizumab. Google Scholar
  78. 78.
    Virkud YV, Wang J, Shreffler WG. Enhancing the safety and efficacy of food allergy immunotherapy: a review of adjunctive therapies. Clin Rev Allergy Immunol. 2018;55:172–89.PubMedCrossRefGoogle Scholar
  79. 79.
    May RD, Fung M. Strategies targeting the IL-4/IL-13 axes in disease. Cytokine. 2015;75:89–116.PubMedCrossRefGoogle Scholar
  80. 80.
    Sastre J, Davila I. Dupilumab: a new paradigm for the treatment of allergic diseases. J Investig Allergol Clin Immunol. 2018;28:139–50.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Bao K, Reinhardt RL. The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine. 2015;75:25–37.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Beck LA, Thaci D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Dupilumab (Dupixent) for asthma. JAMA. 2019;321:1000–1.Google Scholar
  84. 84.
    •• Rial MJ, Barroso B, Sastre J. Dupilumab for treatment of food allergy. J Allergy Clin Immunol Pract. 2019;7:673–4. Case study that shows dupilumab may be a promising treatment for food allergy. PubMedGoogle Scholar
  85. 85.
    Bagnasco D, Ferrando M, Varricchi G, Puggioni F, Passalacqua G, Canonica GW. Anti-Interleukin 5 (IL-5) and IL-5Ra biological drugs: efficacy, safety, and future perspectives in severe eosinophilic asthma. Front Med (Lausanne). 2017;4:135.CrossRefGoogle Scholar
  86. 86.
    Shik D, Tomar S, Lee JB, Chen CY, Smith A, Wang YH. IL-9-producing cells in the development of IgE-mediated food allergy. Semin Immunopathol. 2017;39:69–77.PubMedCrossRefGoogle Scholar
  87. 87.
    Burton OT, Medina Tamayo J, Stranks AJ, Miller S, Koleoglou KJ, Weinberg EO, et al. IgE promotes type 2 innate lymphoid cells in murine food allergy. Clin Exp Allergy. 2018;48:288–96.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Desai M, Oppenheimer J, Lang DM. Immunomodulators and biologics: beyond stepped-care therapy. Clin Chest Med. 2019;40:179–92.PubMedCrossRefGoogle Scholar
  89. 89.
    Stone KD, Prussin C. Immunomodulatory therapy of eosinophil-associated gastrointestinal diseases. Clin Exp Allergy. 2008;38:1858–65.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59:21–30.PubMedCrossRefGoogle Scholar
  91. 91.
    Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115–27.PubMedCrossRefGoogle Scholar
  92. 92.
    Yang YH, Chiang BL. Novel approaches to food allergy. Clin Rev Allergy Immunol. 2014;46:250–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Kim YH, Yang TY, Park CS, Ahn SH, Son BK, Kim JH, et al. Anti-IL-33 antibody has a therapeutic effect in a murine model of allergic rhinitis. Allergy. 2012;67:183–90.PubMedCrossRefGoogle Scholar
  94. 94.
    Liu X, Li M, Wu Y, Zhou Y, Zeng L, Huang T. Anti-IL-33 antibody treatment inhibits airway inflammation in a murine model of allergic asthma. Biochem Biophys Res Commun. 2009;386:181–5.PubMedCrossRefGoogle Scholar
  95. 95.
    Cherie Liu SC, Long A, Lyu S-C, Londei M, Nadeau KC. Randomized controlled phase 2a study results using anti IL-33 in food allergy. J Immunol. 2019;202(1 Supplement):196.1.Google Scholar
  96. 96.
    Varricchi G, Pecoraro A, Marone G, Criscuolo G, Spadaro G, Genovese A, et al. Thymic stromal lymphopoietin isoforms, inflammatory disorders, and cancer. Front Immunol. 2018;9:1595.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936–46.PubMedCrossRefGoogle Scholar
  98. 98.
    Gauvreau GM, O’Byrne PM, Boulet LP, Wang Y, Cockcroft D, Bigler J, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med. 2014;370:2102–10.PubMedCrossRefGoogle Scholar
  99. 99.
    Shin HW, Kim DK, Park MH, Eun KM, Lee M, So D, et al. IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2015;135:1476–85 e7.PubMedCrossRefGoogle Scholar
  100. 100.
    Tang W, Smith SG, Du W, Gugilla A, Du J, Oliveria JP, et al. Interleukin-25 and eosinophils progenitor cell mobilization in allergic asthma. Clin Transl Allergy. 2018;8:5.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Andrew Long
    • 1
    • 2
  • Matteo Borro
    • 1
    • 2
    • 3
  • Vanitha Sampath
    • 1
    • 2
  • R. Sharon Chinthrajah
    • 1
    • 2
    Email author
  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.Department of Internal Medicine, Clinical Immunology UnitUniversity of Genoa and Policlinico San MartinoGenoaItaly

Personalised recommendations