Küçüksezer, UmutÖzdemir, C.Öğülür, İ.Akdis, MubeccelAkdis, Cezmi2022-12-122022-12-122020-09-06Küçüksezer, U. vd. (2020). "Mechanisms of allergen-specific immunotherapy and allergen tolerance". Allergology International, 69(4), 549-560.1323-8930https://doi.org/10.1016/j.alit.2020.08.002https://www.sciencedirect.com/science/article/pii/S1323893020301039http://hdl.handle.net/11452/29805Allergen-specific immunotherapy (AIT) is the mainstay treatment for the cure of allergic disorders, with depicted efficacy and safety by several trials and meta-analysis. AIT impressively contributes to the management of allergic rhinitis, asthma and venom allergies. Food allergy is a new arena for AIT with promising results, especially via novel administration routes. Cell subsets with regulatory capacities are induced during AIT. IL-10 and transforming growth factor (TGF)-beta are the main suppressor cytokines, in addition to surface molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) within the micro milieu. Modified T- and B-cell responses and antibody isotypes, increased activity thresholds for eosinophils, basophils and mast cells and consequent limitation of inflammatory cascades altogether induce and maintain a state of sustained allergen-specific unresponsiveness. Established tolerance is reflected into the clinical perspectives as improvement of allergy symptoms together with reduced medication requirements and evolved disease severity. Long treatment durations, costs, reduced patient compliance and risk of severe, even life-threatening adverse reactions during treatment stand as major limiting factors for AIT. By development of purified non-allergenic, highly-immunogenic modified allergen extracts, and combinational usage of them with novel adjuvant molecules via new routes may shorten treatment durations and possibly reduce these drawbacks. AIT is the best model for custom-tailored therapy of allergic disorders. Better characterization of disease endotypes, definition of specific biomarkers for diagnosis and therapy follow-up, as well as precision medicine approaches may further contribute to success of AIT in management of allergic disorders.eninfo:eu-repo/semantics/openAccessAllergyAllergen-specific immunotherapyImmune regulationImmune toleranceInnate lymphoid cellsInnate lymphoid-cellsHouse-dust miteRegulatory t-cellsDendritic cellsEpicutaneous IimmunotherapyEAACI guidelinesTGF-BETASublingual immunotherapyIntralymphatic immunotherapySubcutaneous immunotherapyImmunologyAllergensAnimalsDesensitization, immunologicHumansHypersensitivityImmune toleranceInflammationArticle0006079069000072-s2.0-8509030856454956069432900655AllergyImmunologySublingual Immunotherapy; Desensitization; AllergoidAllergenCytotoxic T lymphocyte antigen 4Interleukin 10Programmed death 1 receptorTransforming growth factor betaAllergic rhinitisAsthmaBasophil countDendritic cellDisease severityEosinophil countFollow upFood allergyHumanImmune systemImmunological toleranceImmunotherapyLymphoid cellMacrophageMast cellOral immunotherapyPatient compliancePersonalized medicinePriority journalReviewSubcutaneous immunotherapySublingual immunotherapyTreatment durationAnimalDesensitizationHypersensitivityImmunological toleranceImmunologyInflammation