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Mechanisms of Allergen Immunotherapy and Potential Biomarkers for Clinical Evaluation

Sahiner, Umit M., Giovannini, Mattia, Escribese, Maria M., Paoletti, Giovanni, Heffler, Enrico, Alvaro Lozano, Montserrat, Barber, Domingo, Canonica, Giorgio Walter, Pfaar, Oliver·2023·Journal of Personalized Medicine
DOI 10.3390/jpm13050845PMC PMC10223594
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Abstract

Allergen-immunotherapy (AIT) is an efficacious and disease-modifying treatment option for IgE-mediated diseases. Among these allergic rhinitis, insect venom allergy, food allergy, and allergic asthma are the most common candidates for AIT. AIT gives rise to clinical immunotolerance which may last for years after the treatment cessation. Mechanisms of AIT include suppression of allergic inflammation in target tissues and stimulation of the production of blocking antibodies, especially IgG4 and IgA. These mechanisms are followed by a reduction of underlying allergen-specific Th2 cell-driven responses to the allergens. Tolerance induction takes place through the desensitization of effector cells and stimulation of regulatory T cells that show their effects by mechanisms involving cell-cell cross-talk, but also other mechanisms, e.g., by the production of immunomodulatory cytokines such as, e.g., IL-10 and TGF-beta. From a personalized medical perspective, there is a need for clinical biomarkers of value in selecting responders and optimizing patient care during AIT. Also, a deeper understanding of underlying mechanistic processes will improve AIT’s future outcomes. In this paper, the current knowledge of mechanisms in AIT is reviewed with a special focus on biomarkers of this therapy.

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Figure 1 Mechanisms of allergen immunotherapy. Red lines show how allergen immunotherapy inhibits allergic inflammation. Red cytokine levels increase as a result of AIT. Black lines are pathways of allergic inflammation, and black cytokines are those that increase during allergic inflammation. DC reg: Regulatory dendritic cell, ILC2: Innate lymphoid type 2 cell, LTs leukotrienes, PG: prostaglandin, Tfh: T follicular helper cell, nTreg: natural T regulatory cell, iTreg: inducible T regulatory cell, Tfr: follicular T regulatory cell. TSLP: Thymic stromal lymphopoietin.
Figure 1 Mechanisms of allergen immunotherapy. Red lines show how allergen immunotherapy inhibits allergic inflammation. Red cytokine levels increase as a result of AIT. Black lines are pathways of allergic inflammation, and black cytokines are those that increase during allergic inflammation. DC reg: Regulatory dendritic cell, ILC2: Innate lymphoid type 2 cell, LTs leukotrienes, PG: prostaglandin, Tfh: T follicular helper cell, nTreg: natural T regulatory cell, iTreg: inducible T regulatory cell, Tfr: follicular T regulatory cell. TSLP: Thymic stromal lymphopoietin.CC BY · PubMed Central

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Authors
Sahiner, U. M., Giovannini, M., Escribese, M. M., Paoletti, G., Heffler, E., Alvaro Lozano, M., Barber, D., Canonica, G. W., & Pfaar, O.
Venue
Journal of Personalized Medicine
Publisher
MDPI AG
Published
2023-05-17
Volume
13
Issue
5
Pages
845
ISSN
2075-4426
DOI
10.3390/jpm13050845
PMC
PMC10223594
Cited by
66
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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Sahiner, U. M., Giovannini, M., Escribese, M. M., Paoletti, G., Heffler, E., Alvaro Lozano, M., Barber, D., Canonica, G. W., & Pfaar, O. (2023). Mechanisms of Allergen Immunotherapy and Potential Biomarkers for Clinical Evaluation. Journal of Personalized Medicine. https://doi.org/10.3390/jpm13050845