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      Hot topics in allergen immunotherapy, 2023: Current status and future perspective

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          Abstract

          The importance of allergen immunotherapy (AIT) is multifaceted, encompassing both clinical and quality‐of‐life improvements and cost‐effectiveness in the long term. Key mechanisms of allergen tolerance induced by AIT include changes in memory type allergen‐specific T‐ and B‐cell responses towards a regulatory phenotype with decreased Type 2 responses, suppression of allergen‐specific IgE and increased IgG 1 and IgG 4, decreased mast cell and eosinophil numbers in allergic tissues and increased activation thresholds. The potential of novel patient enrolment strategies for AIT is taking into account recent advances in biomarkers discoveries, molecular allergy diagnostics and mobile health applications contributing to a personalized approach enhancement that can increase AIT efficacy and compliance. Artificial intelligence can help manage and interpret complex and heterogeneous data, including big data from omics and non‐omics research, potentially predict disease subtypes, identify biomarkers and monitor patient responses to AIT. Novel AIT preparations, such as synthetic compounds, innovative carrier systems and adjuvants, are also of great promise. Advances in clinical trial models, including adaptive, complex and hybrid designs as well as real‐world evidence, allow more flexibility and cost reduction. The analyses of AIT cost‐effectiveness show a clear long‐term advantage compared to pharmacotherapy. Important research questions, such as defining clinical endpoints, biomarkers of patient selection and efficacy, mechanisms and the modulation of the placebo effect and alternatives to conventional field trials, including allergen exposure chamber studies are still to be elucidated. This review demonstrates that AIT is still in its growth phase and shows immense development prospects.

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          Most cited references215

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              Long-term clinical efficacy of grass-pollen immunotherapy.

              Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment. We conducted a randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective. During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication. Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge. Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells (TH2 cells) (as evidenced by the presence of interleukin-4 messenger RNA). A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease. Scores for seasonal symptoms and the use of rescue antiallergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy, and there was no significant difference between patients who continued immunotherapy and those who discontinued it. Symptom scores in both treatment groups (median areas under the curve in 1995, 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy; P=0.60) were markedly lower than those in the group that had not received immunotherapy (median value in 1995, 2863). Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression. Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity.
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                Author and article information

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                Journal
                Allergy
                Allergy
                Wiley
                0105-4538
                1398-9995
                November 20 2023
                Affiliations
                [1 ] Department of Clinical Immunology Wroclaw Medical University Wroclaw Poland
                [2 ] Faculty of Medicine Transylvania University Brasov Romania
                [3 ] Swiss Institute of Allergy and Asthma Research (SIAF) University Zurich Davos Switzerland
                [4 ] Departments of Medicine and Pediatrics and Division of Allergy and Immunology, Joy McCann Culverhouse Clinical Research Center University of South Florida Tampa Florida USA
                [5 ] Department of Pediatric Respiratory Care, Immunology and Critical Care Medicine Charité Universitätsmedizin Berlin Berlin Germany
                [6 ] Department of Internal Diseases, Pneumonology, Allergology and Clinical Immunology Military Institute of Medicine‐National Research Institute Warsaw Poland
                [7 ] ALL‐MED Medical Research Institute Wroclaw Poland
                [8 ] Section of Rhinology and Allergy, Department of Otorhinolaryngology, Head and Neck Surgery University Hospital Marburg, Philipps‐Universität Marburg Marburg Germany
                [9 ] Allergy and Clinical Immunology National Heart and Lung Institute, Imperial College London London UK
                Article
                10.1111/all.15945
                0494e7df-73e8-4fbe-97b0-bd9ed866a711
                © 2023

                http://creativecommons.org/licenses/by-nc-nd/4.0/

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