A precise etiological diagnosis of seasonal allergic rhinitis (SAR) is essential for a tailored prescription of its only curative treatment, allergen-specific immunotherapy (AIT). This is a challenging task in temperate climates, where most patients are polysensitized to multiple pollen with overlapping seasons.

The study aims to develop a modular, flexible and validated Clinical Decision Support System (CDSS) generated with Artificial Intelligence for the etiologic diagnosis of SAR.

In the context of the @IT-2020 Project, we developed a CDSS for SAR etiological diagnosis. We aimed to automate the CDSS by integrating Machine Learning (ML) algorithms. The CDSS adopts three progressive diagnostic modules: (a) clinical history and Skin Prick Tests (SPT), (b) plus molecular specific Immunoglobulin E (sIgEmol) tests, (c) plus an electronic clinical and environmental Diary. To this end, three raters identified, following international guidelines and a Delphi-like procedure, the culprit pollen on 100 SAR patients in Rome (Italy).

Three models best performing (AUROC >95%) have been then generated by ML training and tested on 2/3 and 1/3 patients, respectively. The validity of the three models was confirmed by: (A) contextual adaptability: as the models' performance was linked to the patients complexity; (B) interpretability: as both, clinical components and sensitization pattern, influenced the models' diagnostic decision (SHAP analysis); (C) geographical generalizability: given the models' equal high performance (AUROC >95%) in diagnosing 92 SAR patients in Tirana (Albania); (D) temporal generalizability: as a high performance was obtained by reducing the patients' monitoring period to 45 days; (E) Allergen Immunotherapy (AIT) prescription adaptability: as the models quite well reproduced the gold standard AIT prescriptions; (F) human-plus diagnostic capability: as the models outperformed 24 doctors in a competition evaluating 12 patients.

In our Proof-of-Concept study, a modular Clinical Decision Support System, based on Machine Learning, replicated with enough reliability raters' diagnosis and AIT prescription in patients with Seasonal Allergic Rhinitis. Further studies are needed not only to target independent replication, but also to prospectively test whether an AI-driven CDSS may be useful to initiate personalized treatment and ultimately improve SAR disease control.

This meta-analysis aims to evaluate the efficacy and safety of allergen-specific immunotherapy (AIT) in treating allergic asthma.

A comprehensive search across PubMed, Cochrane Library, Embase and Web of Science was conducted. Randomized controlled trials (RCTs) evaluating AIT for allergic asthma were included. Data analysis was performed using RevMan 5.3, with evaluations for heterogeneity and publication bias. Subgroup analyses were stratified based on different treatment type, duration, age and allergen type (house dust mites vs. grass pollen).

A total of 28 RCTs were included in the meta-analysis. AIT significantly improved asthma symptoms (p < 0.001), with SCIT showing greater efficacy than SLIT. Treatment duration and age did not significantly impact the outcomes. AIT was effective against both house dust mite and grass pollen allergies. It also notably improved medication scores (p < 0.001) and positively impacted FEV1 (p < 0.001). Regarding safety, AIT did not increase the total number of local side effects but significantly increased systemic reactions.

AIT is effective in improving asthma symptoms and reducing medication use, with subcutaneous immunotherapy being more efficacious than sublingual immunotherapy. The effectiveness varies by allergen type, with no substantial differences across age groups and treatment durations.

Allergen immunotherapy (AIT) is currently the only disease-modifying therapy for allergic airway inflammation. However, its underlying mechanisms remain incompletely understood, which in turn impede the development of more effective and durable treatment strategies. Although animal models are indispensable for mechanistic dissection and therapeutic innovation, they are limited by significant translational gaps arising from fundamental interspecies immunological differences, variability in modeling protocols, and the frequent conflation of short-term desensitization with durable clinical tolerance. This review critically evaluates current animal models of AIT, particularly murine models, by systematically comparing their immunological parameters and treatment paradigms with human clinical pathophysiology. We analyze the effects of animal strain, allergen type, intervention timing, and administration route on the observed mechanisms of tolerance. Furthermore, we assess the utility of these models in optimizing next-generation strategies, including adjuvants and combination biologics. We conclude by proposing a conceptual framework to enhance translational relevance, emphasizing the need for standardized and clinically aligned protocols, integration of chronic and humanized models, and the synergistic use of emerging technologies such as organoids and artificial intelligence. This framework aims to guide the development of predictive preclinical models that can accelerate the rational design of novel AIT therapies.

The oral food challenge (OFC) has long been the reference standard for food allergy diagnosis, as well as to confirm natural development of oral tolerance. The utilization of OFCs has significantly broadened from its role in defining disease to defining participant eligibility, individual allergen reactivity thresholds and treatment outcomes metrics in clinical trials. Adopting OFCs as the sole primary metric to gauge the efficacy of an investigational drug can pose some limitations, such as: creating a barrier to recruitment of representative populations; excluding a vast number of allergic individuals through arbitrary reaction criteria; increasing cost and burden for participants, investigators, institutions, and sponsors; and, most importantly, adding additional risks and/or unpleasant experiences to study participants. A panel of expert allergists was convened by Parexel to discuss the current and future landscape for conducting clinical trials, the role of the OFC and immunologic biomarkers in the context of food allergy clinical trials, and potential innovations for advancing therapeutic development.

Allergen-specific CD4+T cells are a highly heterogeneous population. Depletion of these cells has been proposed as essential to achieve allergen desensitization in allergen immunotherapy.

The overall aim of this study was to characterize the heterogeneity of Timothy grass (Phleum pratense, Phlp) allergen-specific CD4+T cells and determine how the frequency and phenotype of these cells change in response to sublingual (SLIT) and subcutaneous immunotherapy (SCIT). Correlations between frequencies of these cells with Total Nasal Symptom Score (TNSS) and grass-specific serum immunoglobulin were also investigated.

Mass cytometry with lanthanides-tagged pMHCII multimers and CD154 upregulation assays were used to examine changes in the frequency and phenotype of Phlp-specific CD4+T cells in longitudinal peripheral blood mononuclear cell samples from a randomized, double-blind, placebo-controlled trial of SLIT and SCIT. Supervised and unsupervised clustering was used for data analysis.

Phenotypes of Phlp-specific T cells were highly heterogeneous but can be categorized into two major meta-clusters: CRTH2HiCD27Lo and CRTH2LoCD27Hi, each with distinct phenotypic profiles. Weak positive correlations between TNSS and frequencies of T cells within both subsets were observed. SCIT preferentially depleted CRTH2HiCD27Lo cells whereas SLIT depleted CRTH2LoCD27Hi cells. CRTH2HiCD27Lo cell frequency correlated with Phlp-specific IgE and IgG4, but not IgA levels.

Unsupervised clustering revealed distinct subpopulations of allergen-specific T cells that were differentially targeted and depleted by SCIT and SLIT, suggesting that SCIT and SLIT act through overlapping but distinct immunological pathways.

Defining a patient´s allergic profile by identifying the allergens that cause symptoms is essential for the design of specific, tailored immunotherapy, ensuring greater effectiveness in cases of polyallergy. Objective: This observational, multicenter study aimed to demonstrate the heterogeneity of the Spanish population with respiratory allergy by analyzing specific immunoglobulin E (sIgE) patterns for aeroallergens and exploring the relationship between sensitization and clinical symptoms.

A total of 474 patients with respiratory allergy from different regions of Spain were recruited based on their case histories and skin prick test data for aeroallergens. Serum samples were analyzed using ImmunoCAPTM assays to determine sIgE levels for 33 allergenic sources and 43 molecular allergens.

Ninety percent of patients were polysensitized. Pollen was the most common cause of sensitization, followed by mites. Interestingly, polysensitization was significantly associated with the severity of rhinitis symptoms. The molecular diagnosis revealed Phl p 1 as the most prevalent pollen sensitizer. Sensitization to mites was mainly driven by Der p 2. Fel d 1 and Alt a 1 were the most frequently recognized allergens among patients sensitized to animal epithelia and molds, respectively. Moreover, sensitization to mite and animal epithelia allergens was significantly associated with more severe asthma symptoms.

Our findings show a high prevalence of polysensitization and highlight the importance of molecular diagnosis for improving diagnostic accuracy and designing immunotherapy tailored to patients in the region.

Allergen-specific immunotherapy (AIT) is the only intervention capable of modifying the natural course of allergic diseases by inducing long-term immune tolerance. Its clinical efficacy depends on complex regulations of humoral and cellular immunity, yet objective assessment remains hindered by the absence of standardized biomarkers.

This review summarizes recent advances in the immunological mechanisms of AIT and highlights emerging biomarkers—including allergen-specific immunoglobulin G4, regulatory T and B cells, and innate lymphoid cells—that may provide objective measures of efficacy and support individualized treatment strategies. Key messages: (1) AIT uniquely modifies the natural history of allergic diseases; (2) current evaluation relies on subjective measures, highlighting the urgent need for standardized and clinically applicable biomarkers; (3) molecular markers and immune cell subsets offer promising tools for bridging mechanistic insights with clinical endpoints, supporting real-time monitoring and precision-guided optimization of AIT

Named-patient product sublingual immunotherapy (NPP-SLIT) is widely used in France, yet real-world evidence on patient-perceived benefit remains limited.

To assess treatment expectations and patient-perceived benefit over 12-15 months among recent NPP-SLIT initiators using the Patient Benefit Index (PBI) and validated patient-reported outcome measures (PROMs).

ERAPP is a prospective, multicenter, observational study in children and adults with IgE-mediated respiratory allergy. Initiators (≤ 6 months on NPP-SLIT at baseline) completed digital PROMs at baseline, Month 6, and Month 12-15. The primary endpoint was the proportion with PBI ≥ 1 at Months 12-15. Secondary endpoints were changes in PROMs; exploratory analyses examined higher PBI thresholds and item-level fulfillment.

Of 9439 enrolled, 4794 were initiators (950 children; 3844 adolescents/adults). At Month 12-15, PBI ≥ 1 was achieved by 83.8% of children and 84.0% of adolescents/adults. Symptom burden (T5SS) and rhinitis severity (ARIA) improved beyond published MIDs. Asthma control (ACT) improved, whereas changes in rhinitis control (ARCT, ≥ 12 years) and daytime sleepiness (ESS, adults) were below their respective MIDs. Treatment satisfaction (ESPIA-Q11) increased, while adherence (GIRERD) decreased from baseline to follow-up. Nearly half reached PBI ≥ 2 and about one-fifth PBI ≥ 3. Item-level analyses showed highest fulfillment for nasal obstruction relief, improved sleep, and overall symptom relief; fatigue, mood, and social aspects were less frequently fulfilled. Children generally reported slightly higher fulfillment than adolescents/adults.

NPP-SLIT provides sustained, clinically meaningful benefit from the patient's perspective in both age groups. ERAPP supports the PBI as a complementary endpoint that links patient expectations to outcomes and informs patient-centered allergy care.

The first peanut oral immunotherapy (OIT) for children was approved by the US Food and Drug Administration (FDA) in 2020. While clinical efficacy is established, evidence on cost-effectiveness-whether the benefits outweigh the costs and adverse effects-remains limited. A variant of OIT, known as probiotic and peanut OIT (PPOIT), has shown similar efficacy in trials.

To compare the cost-effectiveness of PPOIT, OIT, and no treatment.

This economic evaluation was conducted alongside a multicenter, randomized, placebo-controlled clinical trial in Australia between 2016 and 2019. Time horizon was 10 years, including 1.5 years of active treatment, 2 years of posttreatment follow-up, and 6.5 years of extrapolation. Data were analyzed from May 2024 to August 2025.

PPOIT and OIT.

Effectiveness was measured using remission achieved and patient quality-adjusted life years (QALYs) gained. Costs were evaluated from a health care payer perspective, including active treatment and adverse event costs, and were calculated in Australian dollars. Incremental cost-effectiveness ratios were estimated. Sensitivity analyses were conducted to capture uncertainty.

A total of 201 children aged 1 to 10 years were recruited, 79 in PPOIT, 83 in OIT, and 39 in no treatment (mean [SD] age, 5.9 [2.8] years; 129 [64.2%] male). Over a 10-year horizon, mean (SD) cost per patient was A$3956 (A$67) for PPOIT (treatment, A$3579 [A$0]; adverse events, A$377 [A$67]), A$3582 [A$57] for OIT (treatment, A$3179 [A$0]; adverse events, A$402 [A$57]), and A$249 (A$87) for no treatment (treatment, A$0 [A$0]; adverse events, A$249 [A$87]). Mean (SD) annual remission was 34.1% (12.7%) for PPOIT, 35.1% (15.4%) for OIT, and 7.3% (8.1%) for no treatment. The total QALYs gained for PPOIT, OIT, and no treatment were 0.096, 0.055, and 0, respectively. PPOIT was slightly more costly than OIT, achieved similar remission, and achieved better quality-of-life. Compared with no treatment, both treatments were more costly with minor risks, achieved higher remission (PPOIT, A$1384; 95% CI, A$1269-A$1415; and OIT, A$1199; 95% CI, A$1091-A$1217 per year of remission achieved, respectively), and improved quality of life (PPOIT, A$38 435; 95% CI, A$31 058-A$48 668 and OIT, A$60 840; 95% CI, A$49 479-A$86 531 per QALY gained, respectively).

This economic evaluation found that for remission, both PPOIT and OIT were cost-effective and good value compared with no treatment, with OIT associated with a larger effect size but no clinically meaningful difference. When QALYs are prioritized, PPOIT offers the best value. Key factors associated with cost-effectiveness were treatment product pricing and patient quality of life.

Sublingual and buccal routes offer unique advantages for local and systemic drug delivery. Subcutaneous immunotherapy (SCIT) requires repeated injections of allergens and carries a high risk of adverse effects, whereas sublingual immunotherapy (SLIT) offers a safer, noninvasive, needle-free alternative for allergy treatment. However, compared with SCIT, SLIT typically requires 50-100 times higher allergen doses to achieve clinical effectiveness during allergen-specific immunotherapy (AIT), primarily because of the absence of adjuvants or specialized delivery systems. Promoting the availability of aeroallergens and food allergens to oral dendritic cells (DCs) may increase the effectiveness of AIT while reducing the required doses. Such allergen presentation platforms include adjuvants that stimulate Th1 and/or regulatory T-cell responses. Another strategy involves allergen encapsulation or adsorption into nanoparticulates or mucoadhesive systems to increase allergen availability and target oral DCs. This review examines the physiological factors influencing sublingual/buccal allergen delivery, therapeutic mechanisms and clinical development of approved formulations. Furthermore, we categorize and describe natural or synthetic products used as adjuvants or delivery systems that could be considered as candidate allergen presentation platforms for sublingual and buccal administration.