Allergic rhinitis imposes a substantial clinical and socioeconomic burden globally. While symptomatic pharmacotherapy such as oral antihistamines and intranasal corticosteroids offers temporary relief, allergen immunotherapy provides disease-modifying benefits but requires higher upfront costs. This systematic review synthesises cost-effectiveness evaluations of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) compared to symptomatic pharmacotherapy (SP). A systematic search of electronic databases was undertaken, identifying 35 eligible economic evaluations. Due to methodological heterogeneity, a narrative synthesis was performed. Thirty-two evaluations (91%) concluded that allergen immunotherapy represents a cost-effective intervention, with incremental cost-effectiveness ratios predominantly falling below jurisdictional willingness-to-pay thresholds. Both SCIT and SLIT demonstrated economic value, particularly in patients with co-morbid asthma and when models incorporated sustained post-treatment benefits. Future clinical research should prioritise endpoints that facilitate direct estimation of health utility. Despite diverse healthcare settings and modelling approaches, the evidence supports allergen immunotherapy (AIT) as an economically rational investment. Policymakers should utilise these findings to inform reimbursement decisions.

Sublingual allergen immunotherapy (SLIT) is an effective treatment for immunoglobulin (Ig)E-mediated allergies. Its success is associated with allergen-specific (s)IgG, which blocks IgE-mediated mechanisms. Preventive effects of SLIT in children before allergy-symptom onset remain largely unexplored.

A randomized trial was conducted between October 06, 2017 and December 15, 2022, which included house dust mite (HDM)-sensitized preschool children (aged 3-5 years) showing no allergy symptoms. They were randomized (2:2 blocks) to HDM-SLIT (300 index of reactivity/day, Staloral) or placebo solution for 2 years. Children receiving > 4 months of treatment were included in the analysis. Primary objective of the study was to compare the groups for change in major HDM allergen-Der p 1-sIgG levels from baseline to end of treatment (EOT). Secondary objectives were to compare longitudinal changes (at 4 and 12 months, and EOT) in the (i) levels of HDM-sIgG subclasses and -sIgE using ImmunoCAP/-ISAC and/or ELISA (ii) Der p-reactivity in skin and basophils using skin prick test and basophil activation test (BAT), (iii) sensitization status defined as sIgE-positivity in skin and/or serum, and (iv) Der p-sIgE-blocking activity using inhibition-BAT.

Eighteen children received HDM-SLIT (mean age = 4.26 ± 0.37 years, eight females) and 15 placebo (mean age = 4.16 ± 0.59 years, nine females). HDM-SLIT increased Der p 1-sIgG levels between baseline and EOT versus placebo (effect size = 3.11 [95% CL 1.36-4.82], p = 0.001). Additional changes induced by HDM-SLIT were: increased levels of HDM-sIgG1 and -sIgG4, no long-term increase in HDM-sIgE levels, reduced Der p-reactivity in skin and basophils (p values ≤ 0.05), and blunted development of new sensitizations. Sera from HDM-SLIT treated individuals displayed blocking activity on basophils (p values ≤ 0.05).

Preventive application of HDM-SLIT in allergy-prone children induces immunomodulatory effects early during treatment (elevated sIgG levels with blocking activity and reduced effector cell responses), thereby revealing potential to interfere with allergy.

Allergic diseases arise from aberrant immune recognition of otherwise harmless environmental proteins and are driven by epitope-specific interactions between allergens and the adaptive immune system. Although component-resolved diagnostics have improved molecular characterisation of sensitization, they remain limited to whole-allergen resolution and do not capture the fine specificity and heterogeneity of immune recognition that ultimately determine clinical reactivity, cross-reactivity, and treatment outcomes. Increasing evidence indicates that allergic sensitization, severity, and tolerance are governed by discrete B- and T-cell epitopes rather than entire allergen molecules. This review provides a comprehensive overview of established and emerging technologies for allergen epitope mapping at molecular resolution. For B-cell epitopes, we discuss peptide-based screening approaches, display technologies, deep mutational scanning, structural and biophysical methods, and advances in in silico prediction. For T-cell epitopes, we summarise experimental and computational strategies to identify allergen-derived peptides presented by HLA molecules and recognised by T-cell receptors, highlighting the influence of HLA diversity on individualised immune responses. Finally, we explore the clinical and translational implications of epitope-resolved allergen profiling for next-generation diagnostics, functional cell-based assays, improved risk stratification, cross-reactivity prediction, and the rational design of safer and more precise immunotherapies. Together, these approaches support the development of precision medicine strategies in allergic disease.

Venom immunotherapy (VIT) is a crucial therapy in Hymenoptera Venom Allergy (HVA), but limited data exist on VIT during pregnancy. However, untreated HVA poses a dangerous risk of severe anaphylaxis for both the pregnant woman and her foetus. This study aimed to evaluate the safety and efficacy of maintenance VIT during pregnancy, focusing on spontaneous abortion, preterm birth and adverse events (AEs), compared with rates expected in the general population.

We conducted a prospective, longitudinal, multicentre study across 14 Italian allergy centres, including women who became pregnant while receiving maintenance VIT. Safety outcomes were frequencies of spontaneous abortion, preterm birth and VIT-related AEs during pregnancy. Efficacy was assessed by reactions to field stings. Regression analyses evaluated factors associated with safety and efficacy.

Sixty-eight women with 86 pregnancies were included. Spontaneous abortion occurred in 11 pregnancies (12.8%) and preterm birth in 6 cases (8.1%). These figures were comparable to those in the general population. Older maternal age and previous abortions were associated with abortion in the unadjusted analysis, but no VIT-related characteristics were raised as risk factors. Only one mild, self-limiting AE to VIT occurred during pregnancy. Five women experienced field stings and only one large local reaction was reported, with no subsequent adverse pregnancy outcomes.

Continuation of well-tolerated maintenance VIT during pregnancy was safe and effective, with no increased risk of abortion, preterm birth, or significant AEs and with preserved protection against sting reactions. These findings support continuing maintenance VIT during pregnancy.

The nasal allergen challenge (NAC) is a tool for evaluating upper airway allergic responses. In the CRITICAL study, NAC with cockroach allergen was used to confirm clinical reactivity in sensitized individuals from urban environments before enrollment onto a subcutaneous immunotherapy trial.

Immunologic and transcriptomic predictors of NAC responsiveness were identified.

NAC was performed in 103 participants. Clinical responses were assessed by the Total Nasal Symptom Score (TNSS) and sneeze score (TSNEEZ), which scale positively with symptom severity. Baseline immunologic markers—including skin prick test wheal size, cockroach-specific IgE, IgG, and IgG4, and T-cell responses—were evaluated. Nasal lavage samples were analyzed for gene expression modules. Clinical trial registration: ClinicalTrials.gov NCT03541187.

Larger skin prick test wheal sizes were significantly associated with positive NAC outcomes (2.2 mm larger than negative NAC) and lower reactive doses (hazard ratio = 1.10). Cockroach (i6 extract)-specific IgE levels were inversely correlated with TNSS, while levels of IgE, IgG, and IgG4 specific to the extract used for therapy showed no association. Higher IL-10 T-cell responses were observed in those without reaction, while Bla g 5 and Bla g 9 dominance correlated negatively with TNSS and positively with TSNEEZ, respectively. Transcriptomic analysis revealed that higher expression of eosinophil- and neutrophil-associated modules and lower expression of type 1 interferon, macrophage, and epithelial barrier modules were linked to positive NAC responses.

NAC responsiveness to cockroach extract is influenced by skin test reactivity, T- and B-cell regulation, and nasal gene expression. These findings highlight the role of both adaptive and innate immunity in allergic airway responses and suggest potential biomarkers for clinical reactivity.

The identification of predictive biomarkers for subcutaneous immunotherapy (SCIT) is of great importance for improving its clinical efficacy. This study aims to construct a nomogram predicting the efficacy of SCIT and to evaluate the predictive value of Der p 1 and Der p 2 for SCIT response.

This study included children with allergic rhinitis (AR) and/or asthma (AS) who received house dust mite (HDM) SCIT at Shenzhen Children's Hospital between 2021 and 2024. Baseline characteristics and laboratory data were retrospectively collected before SCIT. The sIgE to HDM components were measured in children's serum before SCIT. The efficacy of SCIT was assessed with VAS scores. Potential predictors for the efficacy of HDM SCIT were identified with logistic regression analysis. A nomogram predicting the efficacy of HDM SCIT was constructed and internally validated.

Among the 209 children who were successfully followed up after one year of treatment, 166 (79%) responded to HDM SCIT, while 43 (21%) were non-responders. Logistic regression analysis identified that Der p (1+2) sIgE, the Der p (1+2) sIgE/tIgE ratio and asthma as predictors of HDM SCIT efficacy. A nomogram predicting the efficacy of HDM SCIT was developed by incorporating the three predictors. The nomogram achieved an AUC of 0.80 (95% CI = 0.72-0.87) and a C-index of 0.80 (95% CI = 0.72-0.87). At a cutoff value of 43.87 kUA/L, Der p (1+2) sIgE achieved an AUC of 0.75, superior to tIgE and the Der p (1+2) sIgE/tIgE ratio.

The Der p 1 and Der p 2 were predictors of HDM SCIT. Der p (1+2) sIgE outperformed both the Der p (1+2) sIgE/tIgE ratio and tIgE in predicting the efficacy of HDM SCIT. A nomogram incorporating Der p (1+2) sIgE, the Der p (1+2) sIgE/tIgE ratio and asthma was developed for the visual and quantitative prediction of HDM SCIT efficacy.

Allergen-specific immunotherapy (AIT) remains the only disease-modifying treatment for IgE-mediated allergy capable of inducing durable disease remission even after cessation of treatment. Conventional AIT delivered by subcutaneous injection is effective but requires long treatment courses and carries a risk of systemic reactions. Mucosal AIT strategies administered by oral, sublingual, or intranasal routes provide a safer, needle-free alternative, but are generally less immunogenic and hence less durable in their effects. Adjuvants have the potential to enhance the efficacy of AIT by improving antigen uptake, activating innate immune cells and/or by suppressing or redirecting pathogenic Th2 immune responses to allergens. This review synthesizes current evidence on how adjuvants might assist allergen immunotherapy, including by induction of regulatory T cells and regulatory B cells, augmentation of blocking IgG and IgA antibodies, and attenuation of IgE-driven effector responses. We survey major adjuvant classes and delivery platforms, including depot carriers, Toll-like receptor (TLR) agonists, nano-emulsions, liposomes, and polysaccharide-based nanoparticles, and summarize findings from preclinical models and early-phase clinical trials. Key translational challenges are considered, including issues of local and systemic safety, route-specific reactogenicity, manufacturing consistency, and regulatory evaluation. Finally, we outline design principles for next-generation adjuvanted AIT vaccines that aim for faster, safer, and more effective immunotherapy, with an emphasis on rational immune targeting and patient-centric delivery formats. Together, these insights highlight key design principles for adjuvanted allergen immunotherapies.

Oral immunotherapy (OIT) has become a cornerstone in the management of IgE-mediated food allergies, offering the potential for desensitization and protection against accidental allergen exposure. However, the therapy carries the risk of adverse effects, notably eosinophilic esophagitis (EoE), a chronic, Th2-mediated inflammatory disorder of the esophagus characterized by eosinophilic infiltration, dysphagia, and esophageal remodeling. This systematic review aimed to identify and summarize all published cases of EoE arising in the context of OIT, characterizing patient demographics, comorbidities, allergens, diagnostic approaches, and treatment strategies.

A systematic search of MEDLINE and Embase from inception to July 1, 2025, was conducted in accordance with PRISMA and Cochrane guidelines. Eligible studies included case reports, case series, cohort studies, and clinical trials describing EoE during OIT. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. Data extracted included patient characteristics, atopic comorbidities, allergen type, OIT regimen, latency to EoE onset, diagnostic modality, and post-diagnosis management. Given the heterogeneity in study design and outcome definitions, a descriptive synthesis was performed.

Thirteen studies (3 trials, 6 cohorts, 2 case series, 2 case reports) comprising 3,655 OIT patients were included. A total of 89 cases of EoE were identified, yielding an overall pooled prevalence of 1.8% (95% CI 0.87-2.79%). Prevalence varied by allergen, with peanut OIT associated with lower risk (0.82%, 95% CI 0.51-1.12%) compared with milk (6.9%, 95% CI 3.74-10.08%) and egg OIT (9.5%, 95% CI 2.78-16.13%). Males accounted for 74% of EoE cases. Diagnosis was confirmed endoscopically in nearly all patients. Most cases improved following proton pump inhibitor therapy and/or discontinuation of OIT, while fewer reports described dietary elimination or topical corticosteroids.

EoE is an uncommon but clinically significant complication of OIT, occurring in approximately 1-2% of treated patients. Male sex, milk and egg OIT, and coexisting atopic disease may increase susceptibility. Recognition of early symptoms, routine monitoring in high-risk patients, and standardized diagnostic criteria are essential to ensure safe and effective OIT implementation. Future prospective studies are needed to clarify risk predictors and establish evidence-based management strategies for EoE in this context.

Subcutaneous immunotherapy (SCIT) is a clinically effective and disease-modifying treatment for house dust mite (HDM)-induced allergic rhinitis (AR). Although SCIT provides long-term symptom improvement for most patients, a subset of patients shows inadequate clinical response. The underlying factors contributing to the heterogeneity in treatment efficacy remain unclear, and robust biomarkers capable of predicting SCIT outcomes are still lacking.

This study aimed to evaluate the clinical efficacy of one-year HDM-SCIT and to identify serum biomarkers associated with therapeutic response, with the goal of improving prediction of SCIT outcomes in patients with AR.

Eligible patients with HDM-induced allergic rhinitis were prospectively enrolled from two medical centers (Peking Union Medical College Hospital and the Affiliated Hospital of Qingdao University) and subsequently completed one year of HDM-SCIT. Symptom severity was evaluated using the visual analog scale (VAS) and total nasal symptom score (TNSS), and quality of life by the rhinoconjunctivitis quality of life questionnaire (RQLQ) at baseline and one year after treatment. Clinical remission was defined as ≥ 30% improvement of VAS and RQLQ scores. In addition, medication scores and TNSS were also included as secondary endpoints to support the response definition. Paired serum samples collected before and after treatment were analyzed using untargeted metabolomics and targeted bile acid profiling based on liquid chromatography-mass spectrometry. To validate metabolomic findings, an HDM-induced AR mouse model was established, followed by SCIT alone or SCIT combined with taurolithocholic acid (TLCA, a bile acid). Nasal histopathology, T cell subsets in the spleen, and cytokine levels in serum and nasal lavage fluid were assessed.

Of the 32 patients who received one-year HDM-SCIT, 22 were responders and 10 were non-responders. No baseline differences in age, AR duration, comorbidities, total IgE, VAS, TNSS, or RQLQ were found between the two groups. However, responders had significantly greater reductions in VAS, TNSS, and RQLQ post-one-year treatment (p < 0.05). Untargeted metabolomics identified 956 differential metabolites (614 upregulated, 342 downregulated) between the pre-treatment group and post-treatment group, 1,389 (582 up, 807 down) and 1,574 (342 up, 1,232 down) between responders and non-responders at baseline and post-treatment, respectively. KEGG analysis highlighted bile secretion as a key differential pathway. Bile acid targeted metabolomics revealed TLCA as a potential biomarker associated with HDM-SCIT efficacy. Mouse models confirmed that HDM-SCIT combined with TLCA, particularly at high dose, alleviated nasal mucosal inflammation (reduced epithelial damage, eosinophils), increased splenic CD4+Foxp3+ regulatory T cells, reduced CD4+IL-4+ helper T 2 cells and serum IgG1, and dose-dependently decreased serum/nasal lavage interleukin (IL)-5, while increasing serum IL-10/interferon-γ.

Serum TLCA levels were associated with clinical response to HDM-SCIT. Animal model validation demonstrated that TLCA may enhance SCIT-induced immune tolerance. These findings support TLCA may serve as a potential metabolite-based biomarker and adjunct target for improving the efficacy of allergen immunotherapy.

This article examines the evolving understanding of β-blockers (BBs) and angiotensin-converting enzyme inhibitors (ACEIs) in the context of anaphylaxis. While once considered relative or absolute contraindications, current evidence shows minimal absolute risk of severe reactions and supports continuation in most patients, particularly when cardiovascular disease is present. For venom and allergen immunotherapies, large studies and guidelines endorse individualized risk-benefit assessment and shared decision-making. Caution remains for patients with unpredictable anaphylaxis, and glucagon may aid adrenaline-resistant cases in BB users. Discontinuation is rarely necessary, with cardiovascular protection usually outweighing theoretic allergic risk.