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

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 IgG1 and IgG4, 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.

The long‐term efficacy of intra‐cervical lymphatic immunotherapy on adults with allergic rhinitis: A randomized controlled study

“…In various studies of conventional immunotherapy, it has been shown that immunotherapy restores the body's immune tolerance to allergens through multiple mechanisms, corrects immune imbalances, downregulates allergen‐specific T and B cell responses and results in decreased IgE production and increased IgG4 production 31 . The latter cannot bind to complements, has limited affinity for Fcγ receptors, and most importantly, it competes with allergen‐specific IgE, thus preventing mast cell and basophil degranulation 31–33 . The hallmark of successful SCIT treatment is demonstrated by an increase in serum‐specific IgE in the beginning, a slow decrease over time, and a decrease in serum‐specific IgE that favors an increase in IgG (especially serum‐specific IgG4) 1,34 .…”

“… 31 The latter cannot bind to complements, has limited affinity for Fcγ receptors, and most importantly, it competes with allergen‐specific IgE, thus preventing mast cell and basophil degranulation. 31 , 32 , 33 The hallmark of successful SCIT treatment is demonstrated by an increase in serum‐specific IgE in the beginning, a slow decrease over time, and a decrease in serum‐specific IgE that favors an increase in IgG (especially serum‐specific IgG4). 1 , 34 Previous studies have shown that the production of allergen specific IgG4 reaction is considered to be a “protective" factor for AIT.…”

Is allergen immunotherapy a model of personalized treatment in pediatric respiratory allergy?

“…IgG-blocking antibodies, specifically IgG1 and IgG4, represent other biomarkers. Their levels can escalate up to 100-fold during AIT, but the correlation with clinical outcomes remains ambiguous [34]. More recent studies have linked specific IgA1 (sIgA1) and specific IgA2 (sIgA2) with successful AIT outcomes [33 ].…”

The Role of Regulatory T Cells in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2024

“…AIT is currently the only treatment with potential longlasting disease-modifying effects for allergic diseases. It consists in the administration of high doses of the causative allergens to induce sustained tolerance after treatment discontinuation, which can be defined as a long-term clinical tolerance upon natural exposure or in vivo challenges [11]. Up to date, AIT is indicated for patients with allergic rhinoconjunctivitis, hymenoptera sensitivity, allergic asthma (only for controlled patients), and some food allergies, especially peanut, cow's milk, and hen's egg allergy [12,189].…”