Allergen immunotherapy (AIT) and dupilumab have been confirmed to improve symptoms of atopic dermatitis (AD); however, the precise immune mechanisms underlying their efficacy and whether they can elicit synergistic immune effects remain not fully elucidated. We aimed to investigate the clinical efficacy and immunological changes in AD patients undergoing AIT, dupilumab, and a combination of AIT and dupilumab treatment.

Clinical data, serum samples, and peripheral blood mononuclear cells (PBMC) were collected from house dust mite (HDM)-sensitized AD patients receiving AIT and/or dupilumab at baseline and after 6 months. Changes in clinical efficacy, HDM-specific IgE and IgG4, serum cytokines, and lymphocyte subgroups were compared among the treatment groups.

A total of 77 AD patients were included, with 39 in the AIT group, 19 in the dupilumab group, and 19 in the AIT combined dupilumab group. The SCORAD scores significantly improved in all groups after 6 months. Levels of HDM-specific IgE and total IgE remained stable in the AIT group but decreased in the dupilumab and combination groups. Levels of IgG4 against major mite components Der p1 and Der p23 increased in the AIT group and combined treatment group. Serum cytokine levels showed no significant changes, except for a decrease in CCL17 in the dupilumab group. Th1/Th2 and Th17/Th2 ratios increased after dupilumab treatment. There were notable differences in T cell subpopulations when PBMCs were stimulated with HDM extracts after 6-month treatment; t-SNE analysis showed the proportion of IL-4+IL-13+CRTH2+ T cells increased in the dupilumab group but had no changes in the AIT and combination group.

AIT, dupilumab, and their combination improved clinical symptoms and quality of life in AD patients. AIT promoted allergen-specific IgG4 production, while dupilumab modulated T cell responses and reduced allergen-specific IgE synthesis. The combination of AIT and dupilumab exhibited the immunological parameter changes characteristic of both treatments but did not result in a significantly greater improvement in AD symptoms.

Allergic disorders are rising in prevalence globally, affecting a substantial proportion of individuals in industrialized nations. The imbalance in the immune system, characterized by elevated allergen-specific T helper 2 (Th2) cells and immunoglobulin E (IgE) antibodies, is a key factor in allergy development. Allergen-specific immunotherapy (AIT) is the only treatment capable of alleviating allergic symptoms, preventing new sensitizations, and reducing asthma risk in allergic rhinitis patients. Traditional AIT, however, faces challenges such as frequent administration, adverse effects, and inconsistent patient outcomes. Nanoparticle-based approaches have emerged as a promising strategy to enhance AIT. This review explores the utilization of nanoparticles in AIT, highlighting their ability to interact with the immune system and improve therapeutic outcomes. Various types of nanoparticles, including polyesters, polysaccharide polymers, liposomes, protamine-based nanoparticles (NPs), and polyanhydrides, have been employed as adjuvants or carriers to enhance AIT's efficacy and safety. Nanoparticles offer advantages such as allergen protection, improved immune response modulation, targeted cell delivery, and reduced side effects. This review provides an overview of the current landscape of nanoparticle-based allergen immunotherapy, discussing its potential to revolutionize allergy treatment compared to traditional immunotherapy.

This review explores the emerging role of T cell exhaustion in allergic diseases and allergen immunotherapy (AIT). It aims to synthesize current knowledge on the mechanisms of T cell exhaustion, evaluate its potential involvement in allergic inflammation, and assess its implications as a novel biomarker for predicting and monitoring AIT efficacy.

Recent studies highlight that T cell exhaustion, characterized by co-expression of inhibitory receptors (e.g., PD-1, CTLA-4, TIM-3), diminished cytokine production, and altered transcriptional profiles, may suppress type 2 inflammation in allergic diseases. In allergic asthma, exhausted CD4+ T cells exhibit upregulated inhibitory receptors, correlating with reduced IgE levels and airway hyperreactivity. During AIT, prolonged high-dose allergen exposure drives allergen-specific Th2 and T follicular helper (Tfh) cell exhaustion, potentially contributing to immune tolerance. Notably, clinical improvements in AIT correlate with depletion of allergen-specific Th2 cells and persistent expression of exhaustion markers (e.g., PD-1, CTLA-4) during maintenance phases. Blockade of inhibitory receptors (e.g., PD-1) enhances T cell activation, underscoring their dual regulatory role in allergy. T cell exhaustion represents a double-edged sword in allergy: it may dampen pathological inflammation in allergic diseases while serving as a mechanism for AIT-induced tolerance. The co-expression of inhibitory receptors on allergen-specific T cells emerges as a promising biomarker for AIT efficacy. Future research should clarify the transcriptional and metabolic drivers of exhaustion in allergy, validate its role across diverse allergic conditions, and optimize strategies to harness T cell exhaustion for durable immune tolerance. These insights could revolutionize therapeutic approaches and biomarker development in allergy management.

Food allergies pose a global healthcare challenge, underscoring the need for effective interventions. This study evaluated the efficacy and safety of epicutaneous immunotherapy (EPIT) for food allergy desensitization.

We conducted a systematic review of randomized controlled trials by searching Ovid EMBASE, PubMed, and Scopus in April 2024. Using a random-effects meta-analysis, we evaluated the clinical effectiveness and harms of EPIT, reporting results as risk ratios with 95% confidence intervals (CI).

After screening 460 abstracts and 35 full reports, 11 were included: nine on peanuts and two on cow's milk (CM). Peanut EPIT had a 51.2% treatment response versus 22.4% for placebo (RR 2.16, CI 1.49-3.12; four studies; moderate certainty). The RR for milk EPIT response rate was 1.78 (CI 1.06-3.00; one study). Five peanut studies (1,396 patients) reported EPIT-related adverse events (RR 1.39, CI 0.94-2.05; low certainty).

EPIT offers a moderate treatment response with a favorable safety profile and significant improvements in quality of life. Current knowledge of EPIT remains limited, with evidence confined to peanut and cow's milk allergies. There is a lack of research on sustained unresponsiveness achieved through food EPIT.

Allergic rhinitis and asthma can be triggered by a variety of aeroallergens, including house dust mites (HDM), tree and grass pollen, and household pets. Identification of the relevant allergen is critical for lifestyle changes and treatments, including allergen immunotherapy. We here assessed the diagnostic performance and clinical utility of a single flow cytometry staining of basophils with major aeroallergen components (AeroDiff CytoBas).

In 156 atopic patients with allergic rhinitis/asthma and 21 non-atopic individuals, allergen-specific IgE levels were determined by ImmunoCAP, and component-specific IgE by ELISA. PBMCs were analyzed by flow cytometry with basophil markers and eight fluorochrome-conjugated allergen component tetramers.

Patients were stratified for sensitization to each of the four allergens. Allergen-component staining in a single multiplex CytoBas assay and component-specific IgE serology performed similarly for Der p 2, Lol p 1, Feld 1, and Can f 1 (ROC AUC: 0.76-0.97 vs. 0.73-0.93). CytoBas had greater diagnostic accuracy than component-specific IgE serology (p < 0.001) for HDM sensitization using Der f 1 or Der p 1, and grass pollen using Lol p 5 or Phl p 1. Furthermore, the combined evaluation of Der p 1 and Der p 2 with CytoBas was 96.3% sensitive and 90.7% specific for HDM sensitization. The combined evaluation of Lol p 1 and Lol p 5 achieved 95.4% sensitivity and 96.4% specificity for rye grass pollen sensitization.

AeroDiff CytoBas has similar to superior diagnostic accuracy compared to singleplex IgE serology, with the additional advantage of a single assay to evaluate multiple allergens. This enables precise and efficient component-resolved diagnosis of aeroallergen sensitization to guide personalized treatment for patients with allergic rhinitis and/or asthma.

Patients with allergic rhinitis (AR) and/or mild or moderate asthma derived from birch-family pollen allergy can be treated with liquid sublingual immunotherapy (SLIT-liquid). This study evaluated the impact of two SLIT extracts on AR and asthma progression or onset in these patients.

This was a sub-analysis of a retrospective, longitudinal comparative cohort study that used a German prescription database. Patients treated with 3-tree (birch/alder/hazel) or birch-only SLIT-liquid and followed up for up to 6 years after treatment were compared with controls dispensed symptomatic medications. Multiple regression analysis compared dispensation data as a proxy for disease status and progression.

A total of 493 patients treated with 3-tree SLIT-liquid and 311 treated with birch SLIT-liquid were analyzed vs. 44,835 patients included as controls. Overall, 70.5% of patients presented solely AR, 24.2% solely asthma, and 5.3% both diseases. Compared with controls, patients treated with 3-tree SLIT-liquid had reduced risk of AR [odds ratio (OR) = 3.21, 95% CI 2.54-4.06, p < 0.001], asthma progression (OR = 2.03, 95% CI 1.43-2.89, p < 0.0001), or asthma onset (OR = 0.592, 95% CI 0.408-0.860, p = 0.006). Birch-only SLIT-liquid showed similar effectiveness in reducing AR and asthma medication dispensation but no significant effect in reducing new-onset asthma.

This real-world study demonstrated the effectiveness of treatment with 3-tree SLIT-liquid or birch SLIT-liquid in slowing the progression of birch-family pollen allergy. 3-tree SLIT-liquid, covering a broader repertoire of epitopes mimicking natural exposure throughout the year, may be valuable for patients sensitized to birch and/or alder and/or hazel pollens suffering from overlapping tree-pollen seasons.

The study aimed to evaluate the level of agreement between specialists in pediatric allergology regarding the diagnosis and indications for pollen allergen immunotherapy (AIT) of polysensitized children in Spain.

A Delphi study was performed using an online survey designed by a committee of pediatric AIT experts: 46 and 44 panelists participated in rounds 1 and 2, respectively. In round 1, 204 statements on 8 dimensions were evaluated (Diagnosis; Therapeutic management; Pollens - Part I; Mites; Moulds; Animals; Hymenoptera venom; and Mixtures - Part II). A total of 148 statements were finally accepted after round 2. Panel members rated their level of agreement with assessments on a 9-point Likert scale based on acceptance by ≥66.7% of them.

According to the results, the polysensitization determination in allergic patients is confirmed by clinical history, skin prick test, total and specific IgE, and molecular diagnostics. Clinical assessments are recommended for the AIT effectiveness evaluation. Follow-ups should be performed 6 months after AIT initiation. According to experts, pollens are the most representative allergens in allergic rhinitis but AIT is more effective in bronchial asthma treatment. The IgE levels are positively related to the intensity of the symptomatology and the efficacy of Grass AIT. In pollen mixtures, a maximum mixture of three AIT allergens is established between Grass, Olive, and Cupressaceae. Mixing pollen from Platanus acerifolia and Parietaria is not recommended.

This study provides, where evidence is lacking, current expert-based opinions on clinical decision-making for managing pollen AIT in polysensitized children.

To determine the molecular sensitization profile of patients allergic to olive pollen and evaluate its correlation with the type and severity of the allergic respiratory disease (ARD).

Observational, cross-sectional study including patients aged 5-55 years with seasonal ARD (rhinitis and/or asthma) due to olive pollen sensitization from the Jaén University Hospital (Jaén, Spain), an area with prolonged high olive pollen exposure. Specific IgE (sIgE) levels to Ole e 1, Ole e 7, and Ole e 9 and clinical variables were considered. ARD severity was categorized according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (rhinitis) and the Guía Española para el Manejo del Asma (GEMA v4.2).

We included 1111 patients (mean [SD] age: 23.4 [12.7] years, 47.7% female) with asthma (87.8%) and rhinitis (96.9%). Ole e 1 sensitization was the most prevalent (79.6%), followed by Ole e 7 (62.0%) and Ole e 9 (50.8%); 60.3% of patients were sensitized to more than 1 olive pollen allergen and 19.2% had negative IgE results. Ole e 1, Ole e 7, and Ole e 9 sensitizations were associated with asthma diagnosis and severity (p < 0.001 for all), Ole e 7 sensitization with rhinitis diagnosis (p = 0.006), and Ole e 1 and Ole e 9 with rhinitis severity (p = 0.007 and p = 0.006, respectively). The Ole e 1, Ole e 7, and Ole e 9 triple sensitization profile was associated with asthma diagnosis (p < 0.001) and severity (p = 0.029), and with rhinitis severity (p = 0.009).

Sensitizations to the olive pollen allergens Ole e 7 and Ole e 9 are prevalent in areas with prolonged high pollen exposure and become major allergens together with Ole e 1. In these areas, a considerable proportion of patients allergic to olive pollen have negative IgE results. Triple sensitization to Ole e 1, Ole e 7, and Ole e 9 is associated with ARD severity and asthma diagnosis. The sensitization profiles based on molecular diagnosis (MD) may affect decisions regarding allergen immunotherapy treatment.

The study aimed to evaluate the level of agreement between specialists in pediatric allergology regarding the diagnosis and indications for allergen immunotherapy (AIT) for dust mites, molds, animal dander, and Hymenoptera venom allergen, as well as mixtures of several allergen sources in polysensitized children in Spain.

A Delphi study was performed using an online survey designed by a committee of pediatric AIT experts: 46 and 44 panelists participated in Rounds 1 and 2, respectively. In Round 1, 204 statements on 8 dimensions were evaluated (Diagnosis, Therapeutic management, and Pollens - Part I; Mites, molds, animals, hymenoptera venom, and mixtures - Part II). A total of 148 statements were finally accepted after Round 2. Panel members rated their level of agreement with assessments on a 9-point Likert scale based on acceptance by ≥ 66.7% of them.

Panel experts recommended molecular diagnosis for dust mite allergy diagnosis in polysensitized pediatrics and mixtures of non-homologous mites (Dermatophagoides and Lepidoglyphus) for optimal AIT management. Subcutaneous AIT with mold extracts is recommended, but no agreement was reached on mixing different mold types. Panel experts agreed that Feld 1 and Can f 1 sIgE are better predictors for animal dander allergy, but no agreement exists on the acceptance of AIT with dander mixtures. Panelists accepted that Apim 2 (hyaluronidase) sIgE indicates Vespid and Apis mellifera cross-reactivity in children; and Apim 4 (melittin) sIgE is a marker of risk for systemic reaction with AIT in Apis mellifera allergy. According to the consensus, SCIT is more suitable for allergen mixtures than SLIT, and agreement was reached for pollen allergens and Alternaria alternata mixtures if stability, safety, and efficacy have been demonstrated.

This Delphi study provides, where evidence is lacking, current expert-based opinions on clinical decision-making for managing polysensitized children.