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Mechanisms and biomarkers of successful allergen-specific immunotherapy

López, Juan-Felipe, Bel Imam, Manal, Satitsuksanoa, Pattraporn, Lems, Sophieke, Yang, Minglin, Hwang, Yu-Kyoung, Losol, Purevsuren, Choi, Jun-Pyo, Kim, Sae-Hoon, Chang, Yoon-Seok, Akdis, Mübeccel, Akdis, Cezmi A, van de Veen, Willem·2022·Asia Pacific Allergy
DOI 10.5415/apallergy.2022.12.e45PMC PMC9669467
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Abstract

Allergen-specific immunotherapy (AIT) is considered the only curative treatment for allergic diseases mediated by immunoglobulin E (IgE). Currently, the route of administration depends both on the different types of causal allergens and on its effectiveness and safety profile. Several studies have reported the mechanisms and changes in humoral and cellular response underlying AIT; however, the full picture remains unknown. Knowledge of who can benefit from this type of treatment is urgently needed due to the patient safety risks and costs of AIT. In vivo or in vitro biomarkers have become a strategy to predict clinical outcomes in precision medicine. There are currently no standardized biomarkers that allow determining successful responses to AIT, however, some studies have found differences between responders and nonresponders. In addition, different candidates have been postulated that may have the potential to become biomarkers. In this review, we aim to summarize the findings to date related to biomarkers in different IgE-mediated allergic diseases (respiratory, food, and venom allergy) with the potential to define who will benefit from AIT.

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Fig. 1 Mechanisms of immune tolerance induction. Tregs, Bregs, ILCregs, and tolerogenic DCs produce immunosuppressive cytokines such as IL-10, TGF-β, and IL-35. Tolerogenic DCs express surface molecules that suppress Th2 and Th17 cells as well as inflammatory DCs, and induce allergen-specific Tregs. Tregs suppress early desensitization of effector cells (eosinophils, mast cells, and basophils), effector Th cells (Th1, Th2, and Th17 cells), inflammatory DCs, ILC2, and allergen-sIgE. Through IL-10, TGF-β, and IL-35 cytokines production, allergen-specific IgA, IgG2, IgG4, and IgD antibodies are released and exert IgE-blocking effects. Bregs suppress effector T cells (Th2 and Th17) and induce Treg cell expansion via the release of IL-10, TGF-β, and IL-35 cytokines. Diverse surface molecules on Breg cells including BCR, PDL-1, CD39, CD73, CD80/CD86, CD40, ICOS-L, and AhR are well-expressed and suppress the inflammatory responses. In autoimmune tolerance, Bregs activate iNKT cells with suppressive function. Moreover, Bregs are also the main producer of allergen-specific IgA, IgG2, IgG4, and IgD antibodies that compete with the cross-linking of allergen-sIgE to effector cells. Tregs, regulatory T cells; Bregs, regulatory B cells; ILC, innate lymphoid cell; DC, dendritic cell; IL, interleukin; TGF, transforming growth factor; sIgE, specific IgE; iNKT, Invariant natural killer T; Ig, immunoglobulin.
Fig. 1 Mechanisms of immune tolerance induction. Tregs, Bregs, ILCregs, and tolerogenic DCs produce immunosuppressive cytokines such as IL-10, TGF-β, and IL-35. Tolerogenic DCs express surface molecules that suppress Th2 and Th17 cells as well as inflammatory DCs, and induce allergen-specific Tregs. Tregs suppress early desensitization of effector cells (eosinophils, mast cells, and basophils), effector Th cells (Th1, Th2, and Th17 cells), inflammatory DCs, ILC2, and allergen-sIgE. Through IL-10, TGF-β, and IL-35 cytokines production, allergen-specific IgA, IgG2, IgG4, and IgD antibodies are released and exert IgE-blocking effects. Bregs suppress effector T cells (Th2 and Th17) and induce Treg cell expansion via the release of IL-10, TGF-β, and IL-35 cytokines. Diverse surface molecules on Breg cells including BCR, PDL-1, CD39, CD73, CD80/CD86, CD40, ICOS-L, and AhR are well-expressed and suppress the inflammatory responses. In autoimmune tolerance, Bregs activate iNKT cells with suppressive function. Moreover, Bregs are also the main producer of allergen-specific IgA, IgG2, IgG4, and IgD antibodies that compete with the cross-linking of allergen-sIgE to effector cells. Tregs, regulatory T cells; Bregs, regulatory B cells; ILC, innate lymphoid cell; DC, dendritic cell; IL, interleukin; TGF, transforming growth factor; sIgE, specific IgE; iNKT, Invariant natural killer T; Ig, immunoglobulin.CC BY-NC · PubMed Central
Fig. 2 Kinetics of immune tolerance induction. AIT dominates the skewing of the T-cell population from allergen-specific Th2 to Treg cells and increases the Bregs population. Both of these cells produce immunosuppressive cytokine IL-10 and suppress allergen-sIgE secretion. In parallel, these cells also induce IgG4 production that displays anti-inflammatory properties. Overall, AIT is considered a successful treatment for allergic inflammation. AIT, allergen immunotherapy; Treg, regulatory T cell; Breg, regulatory B cell; IL, interleukin; sIgE, specific IgE; IgG4, immunoglobulin G4.
Fig. 2 Kinetics of immune tolerance induction. AIT dominates the skewing of the T-cell population from allergen-specific Th2 to Treg cells and increases the Bregs population. Both of these cells produce immunosuppressive cytokine IL-10 and suppress allergen-sIgE secretion. In parallel, these cells also induce IgG4 production that displays anti-inflammatory properties. Overall, AIT is considered a successful treatment for allergic inflammation. AIT, allergen immunotherapy; Treg, regulatory T cell; Breg, regulatory B cell; IL, interleukin; sIgE, specific IgE; IgG4, immunoglobulin G4.CC BY-NC · PubMed Central

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Metadata

Authors
López, J.-F., Bel Imam, M., Satitsuksanoa, P., Lems, S., Yang, M., Hwang, Y.-K., Losol, P., Choi, J.-P., Kim, S.-H., Chang, Y.-S., Akdis, M., Akdis, C. A., & van de Veen, W.
Venue
Asia Pacific Allergy
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-10
Volume
12
Issue
4
Pages
e45
ISSN
2233-8276
DOI
10.5415/apallergy.2022.12.e45
PMC
PMC9669467
Cited by
25
References
3
Language
en
Licence
creativecommons.org/licenses/by-nc/4.0/ (tdm)

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CoChat. (2026). Citation check: Mechanisms and biomarkers of successful allergen-specific immunotherapy. https://app.cochat.ai/papers/10.5415/apallergy.2022.12.e45
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López, J.-F., Bel Imam, M., Satitsuksanoa, P., Lems, S., Yang, M., Hwang, Y.-K., Losol, P., Choi, J.-P., Kim, S.-H., Chang, Y.-S., Akdis, M., Akdis, C. A., & van de Veen, W. (2022). Mechanisms and biomarkers of successful allergen-specific immunotherapy. Asia Pacific Allergy. https://doi.org/10.5415/apallergy.2022.12.e45