Allergen immunotherapy (AIT) is the only disease-modifying therapeutic approach for cat allergy, though it requires at least three years of treatment and can potentially induce severe systemic reactions. Plant-derived bioparticles expressing Fel d 1 allergen (Fel d 1 eBP) have been developed as a novel therapeutic candidate for cat allergy. We aimed to investigate the allergenicity and immunogenicity profile of Fel d 1 eBP.

Fel d 1 eBP was synthesised in vivo in Nicotiana benthamiana and confirmed by cryo-electron microscopy and tomography. Immune modulatory properties of purified natural Fel d 1 (nFel d 1) and Fel d 1 eBP were assessed at T and B cells by flow cytometry in 12 cat-allergic subjects (CA) and 12 non-atopic controls (NAC). Single-cell RNA-seq was used to assess molecular mechanisms of Fel d 1 eBP immune skewing. The safety of Fel d 1 eBP was assessed by measuring basophil responsiveness in whole blood and further confirmed in vivo by its administration as a skin prick test (SPT) in 20 cat-allergic individuals.

Fel d 1 eBP was shown to be a strong inducer of Th1 cells (p < 0.05) and IL-10+ non-Th2 cells (p < 0.05) in CA subjects. Fel d 1 eBP showed a stronger trend for inducing IL-10+ Breg cells compared to nFel d 1, peaking at 3 μg/mL. scRNA-seq analyses demonstrated that Fel d 1 eBP targets the induction of protective metallothionein genes, CCL18+ monocytes and naïve B cells that are interferon responsive and metabolically activated. Moreover, Fel d 1 eBP demonstrated reduced capacity to elicit basophil activation (p < 0.001) and histamine release (p < 0.01), indicating their hypoallergenic nature. Administration of titrated doses of Fel d 1 eBP through skin prick test revealed that they are well-tolerated with reduced mean wheal compared to native Fel d 1 in an open-label Phase 0 study (all, p < 0.001).

We demonstrate that Fel d 1 eBP is hypoallergenic and demonstrates tolerogenic properties, making it a novel candidate for use in AIT for cat allergy.

The management of moderate-to-severe allergic rhinitis (AR) is challenging given numerous advanced therapies. A comparative, evidence-based treatment hierarchy to guide the selection of biologics, allergen immunotherapy (AIT), and advanced pharmacotherapies is critically lacking due to a paucity of head-to-head trials. This network meta-analysis established a treatment hierarchy for moderate-to-severe AR by comparing the efficacy and safety of biologics, AIT, and key pharmacotherapies.

We analyzed 28 randomized controlled trials (13,312 participants), which evaluated the efficacy and safety of biologics (anti-IgE, anti-IL-4Rα therapies), AIT (evaluated within a 6-month time frame to ensure comparability), and key pharmacotherapies (intranasal corticosteroids alone or combined with antihistamines) for moderate-to-severe AR. Efficacy was assessed by changes in the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). A treatment hierarchy was established using surface under the cumulative ranking curve (SUCRA) probabilities.

For the TNSS, anti-IL-4Rα therapy was most effective, followed by anti-IgE therapy and AIT, which surpassed all pharmacotherapies. The combination of intranasal corticosteroid and intranasal antihistamine ranked the highest for ocular symptoms. Anti-IL-4Rα therapy was also superior for improving the RQLQ. Overall, all treatments demonstrated a favorable safety profile. Biologics and AIT did not show a significant increase in adverse events risk compared to placebo.

This network meta-analysis establishes the first comprehensive treatment hierarchy for moderate-to-severe AR. Our findings demonstrate that biologics, particularly anti-IL-4Rα therapy, are the most effective interventions for nasal symptom control, ranking superior to AIT and pharmacotherapies, thus providing a robust, data-driven framework to personalize patient care.

Allergic disorders, including food allergy, asthma, and atopic dermatitis, affect an estimated 10-30% of the global population, with prevalence continuing to rise in industrialized countries. Allergy is driven by dysregulated type 2 T-helper cells (Th2) and immunoglobulin E (IgE) antibody responses. A range of diagnostic tools is available, but most methods are limited by variable sensitivity and specificity, and the inability to predict clinical reactivity. Although allergen-specific immunotherapy (AIT) remains the only etiological therapeutic method for allergic disorders, conventional AITs are limited by frequent administration, risk of adverse events, suboptimal patient adherence, and inconsistent long-term efficacy. Advances in nanotechnology offer emerging opportunities for improving allergy diagnosis and treatment through enhanced analytical sensitivity, targeted allergen delivery and controlled immune modulation. This review provides a comprehensive overview of the latest research on nanomaterials, including their application in nanomaterials-based diagnostic systems and nano-enabled immunotherapies. We highlight their roles in improving allergen-specific IgE detection, refining functional cellular assays, and enabling next-generation immunotherapies through controlled allergen delivery and immunomodulation. We also critically examine key translational barriers and outline essential future directions required for translating nanotechnologies into clinical practice in allergy medicine.

Sublingual immunotherapy (SLIT) efficacy for allergic rhinitis (AR) varies considerably, with 30%-40% of patients showing poor response. A reliable tool integrating multidimensional factors for individualized efficacy prediction remains lacking. This study aimed to construct an optimal prediction model incorporating clinical characteristics, environmental exposure factors, and immune-inflammatory indicators to predict SLIT efficacy in AR patients, and further establish a nomogram as an auxiliary interpretable tool for intuitive clinical application.

A total of 346 AR patients receiving SLIT were included and randomly allocated to training (n = 242) and validation (n = 104) cohorts at a 7:3 ratio. Baseline data included demographics, clinical features, symptom scores, environmental exposures, and immune-inflammatory indicators. Univariate and multivariate logistic regression analyses were performed to screen independent predictive factors. Three models, including random forest, support vector machine, and conventional logistic regression, were developed for performance comparison. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). On the basis of independent predictors, a nomogram was constructed for visual interpretation. Shapley Additive Explanations (SHAP) analysis was further applied to interpret feature importance of the optimal model.

Multivariate logistic regression confirmed these same seven variables as independent predictors of SLIT clinical efficacy in AR: disease duration, baseline symptom score, baseline medication score, air conditioning usage time, specific immunoglobulin E/total immunoglobulin E (sIgE/tIgE) ratio, interleukin (IL)-4, and IL-10 (all P < 0.05). The random forest model yielded optimal predictive performance, while the nomogram built on these predictors achieved acceptable discrimination with AUCs of 0.757 (95% CI: 0.676-0.837) in the training cohort and 0.729 (95% CI: 0.596-0.862) in the validation cohort, and showed better efficacy than the support vector machine (0.739) and conventional logistic regression (0.709) models. Calibration curves demonstrated good agreement between predicted probabilities and observed risks for the nomogram. DCA indicated that the model provided a high clinical net benefit across a wide range of threshold probabilities. SHAP analysis identified disease duration, sIgE/tIgE ratio, and baseline medication score as the three most influential features contributing to model predictions.

The developed random forest model presents good discrimination, calibration, and clinical utility for predicting SLIT efficacy. The corresponding nomogram further enables intuitive individualized clinical assessment, providing a quantitative basis for personalized SLIT decision-making in AR patients.

Early introduction of peanut protein reduces allergy prevalence by approximately 80%, with efficacy diminishing as introduction is delayed. Appropriate prevention involves ingestion of approximately 2 g of peanut protein weekly for infants at low risk and 4 to 6 g weekly for infants at high risk. Population-level implementation that targets all infants achieves greater reduction in disease burden than approaches that target only high-risk groups, although disparities exist among some ethnic groups and groups with restricted access to care. Peanut immunotherapy initiated in younger children (1 to 3 years of age) shows superior efficacy and higher rates of clinical remission as compared with immunotherapy initiated in older children. The natural history of untreated peanut allergy follows a trajectory of increasing peanut-specific IgE levels and clinical reactivity over time, underscoring the importance of early intervention during this narrow developmental window.

Allergen-specific immunotherapy (AIT) is a disease-modifying therapeutic approach that addresses the fundamental etiology of allergic diseases by inducing immune tolerance through modulation of the immune system. Nevertheless, assessing AIT efficacy necessitates long-term treatment, underscoring the need for reliable predictive biomarkers. This review summarizes the recent advances in biomarker research for predicting the effectiveness of AIT, including immunoglobulins, cellular parameters, functional cytokine assays, and provocation tests. This study aims to predict the efficacy of AIT treatment early by classifying and evaluating biomarkers. Combining immunoglobulins, such as sIgE and tIgE, and their ratios, along with cytokine levels (e.g., IL-10, IL-35), could be used to predict clinical efficacy and to construct a composite prediction scoring system for improved accuracy. Monitoring changes in sIgE, sIgG4, sIgG2, cellular markers, and cellular functions (e.g., BAT, ECP, cytokines) should be implemented to assess patient adherence and guide therapy, as they are closely associated with clinical outcomes. Although multiple biomarkers show promising potential, a standardized, unified panel of biological parameters has not yet been established. Future research should integrate multi-omics technologies, combine provocation tests with clinical evaluations, and develop accurate predictive models and more reliable, stable biomarkers for the evaluation of AIT efficacy.

To observe the adverse reactions during standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic asthma (AA) and/or allergic rhinitis (AR), and to analyze the clinical characteristics and potential risk factors.

This single-center retrospective cohort study included 250 children with allergic diseases who received house dust mite (HDM) SCIT treatment at our hospital from July 2022 to July 2025. The participants were divided into a systemic reactions (SRs) group and a non-SRs group. Differences in baseline clinical data and laboratory indicators between the two groups were compared, and independent risk factors for SRs were analyzed using the generalized estimating equation (GEE) method.

Among 250 children (9,244 injections), 114 (45.6%) experienced SRs, with an incidence of 3.47% per injection. SRs were predominantly characterized by immediate, mild grade I reactions, with only 2 cases of grade III reactions and no fatal or serious adverse events. The incidence of SRs during the maintenance period was higher than during the up-dosing period. Univariate analysis showed that the occurrence of SRs was associated with age 5-9 years, AR combined with AA, elevated total immunoglobulin E (IgE), and high Dermatophagoides pteronyssinus (Der p) specific IgE (sIgE) levels (P < 0.05). Multivariate GEE analysis showed that AR+AA comorbidity (compared to AA alone, odds ratio [OR] = 2.219, 95% confidence interval [CI]: 1.061-4.638, P = 0.034) and baseline Der p sIgE ≥ 17.5 IU/mL (OR = 2.233, 95% CI: 1.216-4.099, P = 0.01) were independent risk factors for SRs.

HDM SCIT in children demonstrates a favorable safety profile, with SRs being predominantly mild and dose-dependent. The presence of AR+AA comorbidity (compared to AA alone) and a baseline Der p sIgE ≥ 17.5 IU/mL are key predictors of SR risk. These findings support pre-treatment risk stratification and suggest that children with these risk factors may benefit from a more individualized and monitored SCIT protocol to enhance safety.

Mugwort pollen allergy, largely driven by the major allergen Art v 1, is a major cause of seasonal allergic rhinitis and asthma. Although recombinant allergens enable standardized allergen-specific immunotherapy, clinical data on ultra-short regimens remain limited. We conducted the first-in-human evaluation of an ultra-short recombinant Art v 1 subcutaneous immunotherapy (SCIT) regimen in adults with mugwort-induced allergic rhinitis.

In this randomized, double-blind, placebo-controlled Phase I study conducted outside the pollen season, 30 adults were assigned (1:2:2) to placebo (n = 6) or recombinant Art v 1 formulated with the oil-based adjuvant and administered at cumulative doses of 22 μg (n = 12) or 44 μg (n = 12) over four weekly injections. Primary endpoints were safety and tolerability. Secondary exploratory endpoints included allergen-specific antibody responses, IgE-blocking activity, cytokine production by allergen-restimulated peripheral blood mononuclear cells, and skin prick test (SPT) reactivity.

No deaths, serious adverse events, anaphylaxis, or treatment discontinuations occurred. Adverse events were predominantly mild or moderate and mainly consisted of local injection-site reactions. Both active groups showed marked induction of Art v 1-specific IgG4 and IgG1, increased IgE-blocking activity, and stable total IgE levels. Cytokine profiling demonstrated dose-dependent immune deviation, with increased IL-10 and IL-2 at 22 μg and induction of IFN-γ-associated responses at 44 μg, without activation of Th2-related cytokines. SPT reactivity was reduced in both active groups, with no change in placebo.

An ultra-short recombinant Art v 1 SCIT regimen was safe and induced rapid, dose-dependent allergen-specific immune modulation, supporting further clinical development.

Allergy to Hymenoptera venom is one of the most frequent causes of anaphylaxis in adults. Conventional diagnostic approaches, including skin testing and measurement of allergen-specific IgE (sIgE) to venom extracts, do not always allow for precise identification of the culprit venom. This remains particularly challenging in patients with double-positive or inconclusive conventional test results, which may complicate the decision-making process regarding qualification for appropriate treatment. Component-resolved diagnostics (CRD) and the basophil activation test (BAT) may provide complementary information in such cases and aid in qualification for subcutaneous immunotherapy (SCIT).

In this retrospective registry-based cross-sectional study, 154 adults who had been evaluated for Hymenoptera venom allergy at the Military Institute of Medicine (Warsaw, Poland) between December 2023 and May 2025 were included. Patients were divided into three groups: not qualified for SCIT (n = 27), qualified for bee venom immunotherapy (n = 32), and qualified for wasp venom immunotherapy (n = 95). Serum sIgE to venom extracts and certain components (rApi m 1, m 2, m 3, m 5, m 10; rVes v 1, v 5) were measured. BAT was performed by flow cytometry assessing CD63 expression.

Moderate correlations were found between BAT results and sIgE to rApi m 1 (rho = 0.495; p < 0.001) and rVes v 5 (rho = 0.456; p < 0.001). No correlation was observed for rVes v 1, and negative correlations were noted between rApi m 1 and rVes v 5 in heterologous BAT responses. No statistically significant association was observed between the severity of previous sting reactions and BAT or sIgE parameters. However, due to limited subgroup sizes, these analyses were underpowered and the results should be interpreted as inconclusive.

Among the examined variables, the major components Api m 1 and Ves v 5 were the most strongly correlated with specific basophil activation in vitro. The combined use of CRD and BAT may support clinical assessment and facilitate decisions regarding immunotherapy qualification. Further prospective studies are warranted to assess the prognostic and clinical relevance of our findings.

Alterations in various metabolic pathways observed in patients with allergies suggest that metabolomics offer a precise and comprehensive approach for the diagnosis of allergic diseases and the monitoring of the efficacy of allergen immunotherapy. The purpose of this review is to provide a comprehensive assessment of the existing evidence regarding metabolomic changes in allergic rhinitis and allergen immunotherapy. The PubMed database search was conducted from inception to December 2025. A narrative synthesis was performed. A total of 16 studies were included. Several metabolic pathways are affected in allergic rhinitis, including amino acid metabolism, fatty acid oxidation, and phospholipid metabolism. Additionally, fatty acids, diacylglycerols, and lysophosphatidylcholines have emerged as potential diagnostic and severity biomarkers for allergic rhinitis. Allergen immunotherapy has also been shown to modulate these metabolic disturbances. Notably, arachidonic acid, linolenic acid, and sphingosine may serve as indicators of therapeutic efficacy. In conclusion, allergic rhinitis is characterized by distinct metabolic alterations, mainly involving lipid metabolism. Allergen immunotherapy has been shown to modulate these metabolic disturbances. Future research should focus on integrating metabolomics with clinical and other molecular approaches to enhance their clinical applicability in allergic rhinitis.