Allergen immunotherapy (AIT) is a well-established treatment with demonstrated efficacy and safety. However, variability in study outcomes remains a challenge, driven by differences in patient characteristics, study designs, and treatment durations. Moreover, disparities in allergen composition and quality of AIT products across manufacturers contribute to significant heterogeneity, complicating the interpretation of efficacy and safety data. This meta-analysis focuses on assessing the efficacy and safety of a single manufacturer's liquid sublingual immunotherapy (SLIT) for allergic rhinoconjunctivitis (ARC). By narrowing the scope to one specific product, this study seeks to reduce variability linked to product differences, aligning with recommendations from the World Allergy Organization to improve the reliability of meta-analytic findings.

Randomized controlled trials (RCTs) on index of reactivity (IR) SLIT liquid formulations of various allergens were identified through comprehensive searches in electronic databases (MEDLINE, ISI Web of Science, the Cochrane Library, and ClinicalTrial.gov) up to December 2024, complemented by manual searches. Data on populations, treatments, and outcomes were extracted. Efficacy was evaluated by calculating the standardized mean difference (SMD) for symptoms and medication use. Subgroup analyses were performed by age, allergen type and sensitization status. Asthma comorbidity, dose and duration of SLIT were evaluated using meta-regression.

A total of 25 RCTs (1,830 patients) provided data on symptom scores (SS), and 19 RCTs (1,555 patients) reported on medication scores (MS). Analysis revealed that IR-SLIT-liquid was significantly more effective than placebo in reducing both SS (SMD: -0.30; 95% CI: -0.41 to -0.18; P < 0.0001) and MS (SMD: -0.51; 95% CI: -0.72 to -0.29; P < 0.0001). Efficacy outcomes were consistent regardless of factors such as age, allergen type (grass, house dust mites, trees, weeds), sensitization status, asthma presence, or cumulative dose, while longer treatment durations were associated with improved efficacy. No significant adverse events were reported.

This meta-analysis underscores the clinical effectiveness and safety of IR-SLIT-liquid, confirming its role as a reliable etiologic treatment for patients with ARC, for all allergens and age groups. The effect size is comparable to other immunotherapy options. The low rates of adverse events and treatment withdrawals highlight favorable tolerability and high level of patient adherence.

The efficacy of Hymenoptera venom immunotherapy is contingent upon the accurate identification of the insect responsible for the allergic reaction. The techniques used to detect specific IgE suffer from difficulties due to the cross-reactivity between Hymenoptera venoms (false positives), diagnostic ability, and the limited availability of allergenic components (false negatives). In this study, we analyzed the discrepancies in the results obtained with Euroline® DPA-Dx and ImmunoCAP® in the diagnosis of allergic reactions due to Hymenoptera stings in 151 patients. The results (positive/negative) of ImmunoCAP® and Euroline® agreed in 77/151 (50.99%) cases; with 15/151 (9.93%) cases positive for the same insect, and 61/151 (40.4%) cases positive for multiple insects. When the results were used to decide which venom to use for immunotherapy, there was a statistically significant discrepancy for Polistes dominula (21.8% of cases with ImmunoCAP® compared to only 8.4% with Euroline®). The presence of Polistes venom phospholipase (Pol d 1) in Euroline® did not increase its ability to differentiate double sensitization to wasps. ImmunoCAP® and Euroline® exhibited comparable diagnostic performance in bee venom allergy. For vespid venom allergy—particularly involving Polistes species—ImmunoCAP® appeared to show a slight diagnostic advantage, although this finding should be interpreted with caution.

Cow's milk allergy (CMA) is one of the most common causes of food allergies (FA) in children. There have been studies on the use of immunotherapy in cow's milk protein allergy, with oral immunotherapy (OIT) being the most extensively researched. We conducted a comprehensive analysis of randomized controlled trials (RCTs) to explore the efficacy and safety of OIT to manage cow's milk allergy in children.

PubMed, EMBASE, Cochrane Library, and Scopus databases were searched from their inception until August 2024. Randomized controlled trials that reported on the efficacy or safety of IT for CMA were included. Two investigators independently extracted data on regimen of intervention, outcomes, number of cases and gender ratio. Pooled estimates of relative risks or standardized mean differences with 95% confidence intervals were calculated from the included studies for dichotomous and continuous outcomes.

Nineteen RCT articles (815 participants) were included. The meta-analysis indicated that oral immunotherapy significantly facilitated desensitization in patients with cow's milk allergy in children (relative risk [RR] 2.51, 95% CI: 1.54–4.09, I²=84.4%). Tolerance threshold at oral food challenges (OFC) increased following oral immunotherapy compared with a standard mean difference (SMD) of 3.58 (2.82–4.33). After oral immunotherapy, the antibody titers of cow milk protein sIgE (SMD -0.42, 95% CI: -0.72 to -0.11, I²=28.8%) and casein sIgE (SMD -0.54, 95% CI: -0.97 to -0.11, I²=0%) decreased. The risk of adverse reactions with immunotherapy was not higher than that in the control group, with an RR of 2.05 (95% CI 0.96–4.37, I²=81.5%).

Oral immunotherapy is associated with desensitization to CMA in children, without increased risk of short-term adverse events, but late complications such as eosinophilic esophagitis require caution. More high-quality studies are needed to explore the long-term efficacy of OIT for CMA.

Hen's egg (HE) is a major food allergen in children. Oral immunotherapy (OIT) has emerged as a promising therapeutic option for hen's egg allergy (HEA), but the precise immunological mechanisms underlying HE-OIT are not fully understood.

We aimed to investigate the systemic immune phenotype in children with HEA and to examine transcriptomic changes during HE-OIT.

We enrolled 16 children, aged between 3 and 12 years, diagnosed with HEA (median age, 4.5 years). Peripheral blood mononuclear cells were collected before the initiation of HE-OIT and after the completion of the build-up phase. The transcriptomics of the samples were analyzed using single-cell RNA sequencing.

All eight patients (8/8) whose blood samples were collected after the build-up phase achieved desensitization to 60 g of boiled HE white (6.0 g of HE proteins). Following the OIT build-up phase, significant reductions in total CD4+ T cells and early activated CD4+ T cells were observed (P = 0.001 and 0.045, respectively), while the frequencies of late activated CD4+ T cells and fully activated CD8+ T cells were increased (P = 0.019 and 0.038, respectively). Clonal analysis revealed proliferation within the late activated CD8+ T cell subset following OIT, indicative of the exhausted state of CD8+ T cells. Additionally, the population of regulatory T cells with abundant IKZF2 expression was significantly increased after the OIT build-up phase.

HE-OIT was associated with systemic immune cell transcriptomic changes, suggesting that its efficacy derives from these immune alterations.

The mechanisms underlying immune tolerance induction during sublingual immunotherapy (SLIT) of seasonal allergic rhinitis (SAR) remain insufficiently understood. This study aimed to investigate the molecular and immunological process involved in SLIT. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to examine the functions of differentially expressed genes (DEGs) in leukocytes from 11 SAR patients at three time points: baseline, peak pollen phase (PPP), and end-of-treatment. Patients received a 4-month SLIT course with Artemisia annua (A. annua) extract (n = 5) or placebo (n = 6). Plasma cytokine levels were measured in a validation cohort of 15 SAR patients (9 in the SLIT group and 6 in the placebo group) using Luminex assays. The results showed that A. annua SLIT inhibited the upregulation of IL-17A-associated pathways and the expression of inflammatory mediators, including CXCL1, CCL7, and PLPP3, while enhancing myeloid immune cell function by increasing the expression of CD36, TYROBP, FCGR1A, and FCER1G. Additionally, A. annua SLIT reactivated myeloid immune cell-associated genes that were downregulated during PPP and significantly reduced IL-17A and GRO-β levels in plasma, compared to the placebo group. These findings suggest that A. annua SLIT alleviates SAR by modulating IL-17A pathways, reducing inflammatory responses, and enhancing myeloid immune cell function.

House dust mites (HDMs) are a major source of indoor allergens, significantly contributing to allergic rhinitis, asthma and atopic dermatitis. This review examines the epidemiology, microbiological classification and pathophysiology of HDM allergy, highlighting key allergens such as Der p 1, Der p 2 and Der p 23. Furthermore, we discuss the pivotal role of allergen-specific immunotherapy (AIT), the only disease-modifying treatment for immunoglobulin (Ig)-E disease. Recent studies have identified predictive biomarkers for allergen-specific immunotherapy (AIT) efficacy, including the specific IgE to total IgE (sIgE/tIgE) ratio and regulatory follicular T cell profiles, supporting a more personalized approach to therapy. Additionally, emerging immunotherapy strategies, such as recombinant allergens and peptide-based formulations, aim to improve safety and clinical outcomes. As HDM allergy prevalence rises globally, further research into optimizing diagnostics and treatment strategies remains crucial for enhancing patient care.

The present study aimed to compare the correlation between serum brain-derived neurotrophic factor (BDNF) level and clinical, immunological parameters in patients receiving allergen-specific subcutaneous immunotherapy (SCIT) for 3 years duration.

Comparing serum BDNF levels in AR patients and healthy controls, the correlation between serum BDNF level and clinical parameters in AR patients was analyzed further. Immunological parameters, including total IgE, d1 sIgE and d2 sIgE, serum BDNF levels, and the clinical parameters were evaluated at the 4-time points that including before immunotherapy, the end of the 1st, 2nd, and 3rd year during the SCIT treatment for AR patients who received immunotherapy.

We found a significantly elevated expression level of serum BDNF levels in AR patients and it also showed a significant correlation with nasal symptom score that included itching score, nasal obstruction score, runny nose, total nasal symptom score, and peripheral parameters including eosinophil percent and eosinophil count. For AR patients who received immunotherapy, a good response was shown, the expression of serum BDNF levels showed a downward trend during 3 years of SCIT, and it significantly positively correlated with the improvement of nasal symptoms including nasal obstruction, nasal itching, and medicine score.

Serum BDNF level was associated with clinical severity in AR patients and clinical parameters in AR patients in SCIT duration, which should be considered as a response evaluation biomarker to monitor clinical efficacy in allergen-specific immunotherapy.

In a clinical trial of allergen-specific immunotherapy for allergic rhinoconjunctivitis, the Combined Symptom Medication Score (CSMS) was utilized as the primary endpoint. This was aligned with the European Academy of Allergy and Clinical Immunology recommendation. However, participants wanted to elaborate on how their behaviour affected their score, so voluntary free text boxes were added to the CSMS questionnaire. This study aimed to evaluate the patient-reported outcomes registered in the free text boxes to identify and understand contexts and mechanisms that may affect the CSMS.

The realist evaluation methodology was followed in four iterative steps: 1) development of the initial programme theory and context-mechanism-outcome (CMO) configurations, 2) collection of evidence, 3) data analysis, and 4) interpretation and assessment of results.

Seven CMO configurations were identified, highlighting contexts and mechanisms that may affect the CSMS. These included CMO1 - decision on preventive relief medication dosage, CMO2 - exhibiting symptom-relieving behaviour, CMO3 - being exposed to different levels of grass pollen, CMO4 - mistaking other symptoms for grass pollen-induced symptoms, CMO5 - different exposure to grass pollen when travelling abroad, CMO6 - reporting of relief medication for other allergies in CSMS, and CMO7 - failure to report symptoms not included in CSMS.

This realist evaluation contributes verified CMO configurations based on patient perspectives to understand how context and mechanisms may affect the CSMS. We recommend further investigation in quantitative studies, as awareness of these CMOs may increase the internal validity of future allergy trials using CSMS as an endpoint.

Allergen immunotherapy is the sole therapeutic option capable of modifying the natural course of allergic rhinitis and preventing the development of asthma. Results from paediatric patients are scarce. To evaluate the effectiveness and safety of a glutaraldehyde-modified extract of mites (Beltavac®) administered for one year under clinical routine conditions in children between 3 and 11 years old.

This was a multicentre, prospective, 13-month cohort study. Among 97 children diagnosed with immunoglobulin E-mediated house dust mite allergic rhinoconjunctivitis, 87 initiated the subcutaneous immunotherapy. The main outcomes included the Combined Symptoms and Medication Score (CSMS), assessed for 1 month at baseline and after 1, 6, and 12 months, and the number of adverse reactions according to the WAO adverse reaction grading system. The levels of serum-specific immunoglobulins were also assessed.

CSMS improved scores throughout therapy (adjusted mean change and 95% confidence interval: 0.55, 0.26-0.84 points; p< 0.001). Improvements occurred in both children with (n = 68) and without asthma (n = 19), as well as in children aged ≥6 years (n = 76) and <6 years (n = 11), although statistical significance was not reached in the smallest subgroups. Eight children (9.2%) developed a total of 15 adverse reactions. Most occurred after the initial dose (five out of eight children), and were local (six out of eight) and minor (five out of eight). Over 90% of patients completed the full regimen.

This study supports the effectiveness and safety of allergen immunotherapy administered according to a rush schedule for one year for paediatric allergic rhinitis.

Allergen immunotherapy (AIT) is a key therapeutic approach for allergic rhinitis and asthma, demonstrating the ability to modify disease progression by targeting type 2 inflammation. This study evaluates the efficacy of a mobile application (app/web platform) AllergyVax®, designed to implement a patient-centered care (PCC) strategy to increase patient engagement in the treatment. A retrospective cross-sectional analysis was conducted with 482 patients diagnosed with respiratory allergic diseases who initiated sublingual immunotherapy (SLIT). Participants were divided into 2 groups: Group A received standard information, while Group B utilized the AllergyVax® app for managing treatment. This app provided daily reminders, evaluated symptom control through standardized questionnaires, and facilitated communication between patients and healthcare providers. Results indicated a significant increase in adherence rates among app users, with 92.11% adhering to SLIT compared to 46.32% in the non-app group. The app users exhibited a 2.42 times greater likelihood of maintaining adherence and reduced dropout rates by 82%. The AllergyVax® app improved adherence across all demographics, emphasizing the importance of innovative digital tools in enhancing patient engagement and treatment outcomes. In conclusion, this study highlights the critical role of mobile technology in promoting adherence to SLIT, suggesting that integrating digital solutions into AIT can lead to better management of allergic diseases and improved patient outcomes.