Immunotherapy in Allergic and Mixed Rhinitis.

Peanut allergy is a significant rising public health problem affecting both children and adults. Early peanut introduction has been adopted in multiple westernized nations as a preventative strategic measure to reduce the risk of developing peanut allergy, although implementation faces barriers. Multiple therapies to treat peanut allergy have been developed, including oral immunotherapy and omalizumab as approved treatments to provide protection against reactions from accidental exposure and reduce the risk of anaphylaxis, offering options beyond strict avoidance. Strategies in the developmental pipeline include epicutaneous immunotherapy and sublingual immunotherapy. The future is bright for individuals with peanut allergy, as these breakthroughs can help address the fear, uncertainty, severity, and lack of protection that has become synonymous with this disease. Shared decision-making is needed to ensure that each patient receives the management approach best suited to their needs, preferences, and goals.

The gut microbiota plays a crucial role in modulating mucosal immunity and allergic responses, yet its predictive value for sublingual immunotherapy (SLIT) outcomes remains underexplored in Artemisia pollen-induced allergic rhinitis (AR). In this single-center prospective cohort study, 204 adults with Artemisia pollen-induced AR underwent baseline stool collection before initiating standardized SLIT. Gut microbiota was analyzed using 16S rRNA sequencing of the V3-V4 region, with prespecified features including Shannon diversity index, composite abundance of butyrate-producing bacteria (Faecalibacterium, Roseburia, Eubacterium rectale group), and Prevotella-to-Bacteroides (P/B) ratio. Clinical response was defined as ≥30% reduction in combined symptom-medication score (CSMS) during the peak pollen season. We developed three prediction models: Model A (clinical variables only), Model B (clinical variables plus microbiota features), and Model C (parsimonious model via L1 regularization). The response rate was 54.41% (111/204). In multivariable analysis, all three microbiota features independently predicted treatment response: butyrate-producing bacteria (OR = 1.59, q = 0.006), P/B ratio (OR = 1.43, q = 0.020), and Shannon diversity (OR = 1.33, q = 0.046). Model B demonstrated superior discrimination compared to Model A (AUC 0.79 vs 0.71, ΔAUC = 0.08, P = 0.021), with improved calibration (intercept α = -0.03, slope β = 0.98) and significant net reclassification improvement (NRI = 0.36, P = 0.002). Decision curve analysis confirmed greater net benefit across clinically relevant threshold probabilities. The parsimonious Model C maintained good performance (optimism-corrected AUC = 0.78) with 77.48% sensitivity and 72.04% specificity. Baseline gut microbiota characteristics, particularly butyrate-producing bacterial abundance, microbial diversity, and Prevotella/Bacteroides community structure, significantly predict SLIT response in Artemisia pollen-induced AR and provide substantial incremental value over conventional clinical parameters. These findings support the integration of gut microbiota assessment into pretreatment stratification algorithms for allergen immunotherapy.

House dust mite (HDM) allergy significantly impacts quality of life. Allergen immunotherapy (AIT), specifically sublingual immunotherapy (SLIT), is an effective treatment for HDM allergy, but adherence to SLIT remains a challenge. This study aimed to evaluate the impact of adherence to SLIT on the use of allergy medications, including antihistamines, nasal corticosteroids, and inhaled corticosteroids (ICS) in a real-world setting. We conducted a nationwide cohort study using data from Denmark's comprehensive registries. Patients who initiated HDM SLIT between 2015 and 2020 were included, with follow-up through 2022. Adherent patients, defined as those obtaining at least 80% of the prescribed Defined Daily Dose (DDD) of SLIT, were compared to non-adherent patients. Medication use was tracked for antihistamines, nasal corticosteroids, and ICS. Statistical analyses, including Probit and generalised linear models, assessed the likelihood of obtaining medications and the quantity dispensed, adjusted for age and sex. Of 950 patients, 456 (48%) were classified as adherent. Adherent patients showed significantly reduced usage of antihistamines (p < 0.001) and nasal corticosteroids (p < 0.001) compared to non-adherent patients. No significant differences were found in ICS use or dosage. Additionally, adherent patients were more likely to have higher education levels and be married or cohabiting. Adherence to SLIT for HDM allergy is associated with reduced use of antihistamines and nasal corticosteroids. These findings emphasise the importance of SLIT adherence in managing HDM allergy and suggest that improving adherence could further reduce medication usage, improving patient outcomes in real-world settings.

To evaluate the efficacy differences of house dust mite sublingual immunotherapy in allergic rhinitis patients of different ages. Ninety-two patients who underwent 1 year of house dust mite sublingual immunotherapy were retrospectively analysed and divided into groups of children (<14 years, n = 46) and adolescents and adults (≥14 years, n = 46). The total nasal symptoms, total medication, combined symptom and medication, and mini Rhinoconjunctivitis Quality of Life Questionnaire scores were assessed. Significant improvements were displayed after sublingual immunotherapy treatment compared with baseline (p < 0.001). In particular, children exhibited more pronounced improvements on each indicator than adolescents and adults at the end of 1 year of sublingual immunotherapy treatment (p < 0.05). Meanwhile, correlation analysis revealed that the mini Rhinoconjunctivitis Quality of Life Questionnaire score has positive correlations with the total nasal symptoms, total medication, and combined symptom and medication scores (all p < 0.001). More notable improvements were seen in children than in adolescents and adults with allergic rhinitis after one year of house dust mite sublingual immunotherapy treatment.

Patient characteristics and treatment satisfaction with 300 IR sublingual allergen immunotherapy for cat allergy: Results from a French survey

Tablet formulations of allergen extracts are widely recommended over other formulations for the sublingual immunotherapy (SLIT) of respiratory allergies. However, with adequate clinical trial evidence, SLIT (liquid) drop formulations may be a relevant allergy treatment option. The RHAPSODY multinational, Phase III, parallel-group, double-blind, placebo-controlled, randomised clinical study of adults with moderate-to-severe, grass-pollen-induced allergic rhinoconjunctivitis (ARC) with or without asthma was conducted at 45 investigating centres in six European countries. Participants received 26 months of continuous treatment with active 5-grass-pollen SLIT drops or placebo. The primary efficacy endpoint was the average daily total combined score (TCS, comprising a symptom score and a rescue medication score) during the second peak grass pollen season (PGPS). Of the 445 randomised patients (mean ± standard deviation (range) age: 32.6 ± 9.9 (18-63); males: 55.1%), 389 completed the trial. The primary efficacy endpoint showed a statistically significant difference in favour of active treatment versus placebo (average difference in the daily TCS: 1.88 (95% CI: 0.60-3.17); relative difference 26.51% (95% CI: 9.42-40.55); p = 0.0036). The difference (0.17 points) in the average weekly Rhinitis Quality of Life Questionnaire score during the second PGPS in favour of the active treatment was clinically relevant but not statistically significant. The differences in efficacy were generally driven by the medication score, rather than the symptom score. Most adverse events were mild and local. RHAPSODY was the first well-powered clinical trial to show the positive risk-benefit ratio of 5-grass-pollen SLIT drops in adult participants with moderate-to-severe grass-pollen-induced ARC.

Food allergy is an increasing public health concern characterized by inappropriate Th2-driven immune responses to otherwise harmless food antigens, leading to IgE-mediated hypersensitivity. Current management strategies rely on allergen avoidance and emergency interventions, which fail to address the root cause of immune dysregulation. Given the central role of helper T cells, particularly Th2 and regulatory T cells (Tregs), this systematic review evaluates the efficacy, safety, and immunological effects of three T cell-targeted allergen-specific immunotherapies: oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT). Thirteen studies, comprising 14 study arms, from four databases were included following PRISMA 2020 guidelines and PICOS-based selection. Based on the study design, RoB 2 and ROBINS-I tools were used to evaluate risk of bias. OIT demonstrated strong clinical and immunological outcomes, with high desensitization and sustained unresponsiveness (SU) rates, increased FOXP3⁺ Tregs, and suppression of Th2 cytokines (IL-4, IL-5, IL-13). SLIT showed moderate immunomodulatory effects with better tolerability, while EPIT provided the safest profile but limited T cell reprogramming. Overall, this review highlights the therapeutic potential of targeting T cells in food allergies and supports the use of OIT as the most effective current strategy, despite a higher risk of adverse events. While SLIT and EPIT remain promising, particularly in pediatric populations, further research is needed to enhance durability, personalize treatments, and combine immunotherapies with adjuncts such as biologics or Treg-promoting agents to achieve lasting immune tolerance. PROSPERO registration ID: CRD420251012358.

The European Academy of Allergy and Clinical Immunology (EAACI) established a Task Force to assess the existing data on the relationship between eosinophilic esophagitis (EoE) and allergen immunotherapy (AIT). This systematic review and meta-analysis aimed to study the incidence of confirmed EoE, developing as a side effect of AIT to food or airborne allergens, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. The literature search was performed in three databases (PubMed, Embase and Scopus). Databases were searched from inception to March 31st, 2023. A total of 17 studies met the criteria for inclusion in the review. Fifteen studies, comprising 3,302 patients, were on food desensitization, and the overall estimate of EoE incidence, combining the results of these individual studies, was 2.31% (95% CI 1.45, 3.36). Registered data reported de novo cases of eosinophilic esophagitis, and its diagnosis was usually made during the maintenance phase of food desensitization. With the adopted searching strategy, only two studies on sublingual immunotherapy with aeroallergens meeting the inclusion criteria were retrieved, comprising 1,436 patients and not reporting cases of EoE. The meta-analysis showed that the development of EoE is a common adverse effect of oral immunotherapy with food allergens, whereas it is uncommon during sublingual immunotherapy with aeroallergens. Trial Registration: PROSPERO: CRD42023425917.

A retrospective cohort study on the association between allergic rhinitis, sublingual immunotherapy, and COVID-19 symptomatology.

Shellfish allergy is among the most common food allergies (FAs) worldwide and represents a severe immunoglobulin E (IgE)-mediated FA with tropomyosin functioning as the predominant pan-allergen. Current management of shellfish allergies is strictly palliative with allergen avoidance, underscoring the critical need for disease-modifying therapies. While conventional allergen-specific immunotherapy (AIT) approaches, namely oral and sublingual immunotherapies, demonstrate capacity for desensitization, more clinical applications are needed in the potential safety concerns and prolonged treatment durations. Innovative treatments, such as the design of modified shellfish allergens, DNA vaccine technologies, and nanoparticle-based delivery platforms such as virus-like particles (VLP), show efficacy and potential in inducing protective antibodies while promoting antigen-specific immune tolerance with reduced allergenic risks. These innovative approaches hint at a promising pathway in achieving safe, effective, and long-lasting clinical tolerance for shellfish allergy. This review describes the current perspectives on allergen immunotherapy regarding shellfish allergy and analyzes emerging therapeutic strategies poised to overcome these limitations.

The retrospective study EfficAPSI explored the real-world impact of liquid sublingual allergen immunotherapy (AIT; Staloral® SLIT-liquid) on health care resource utilization (HCRU) in allergic rhinitis (AR) patients with/without asthma. In the EfficAPSI cohort, patients dispensed SLIT-liquid and AIT-naïve controls taking symptomatic drug treatment (SDT) were compared using propensity score weighting. A total of 5 periods were analyzed, namely, the historical pre-SLIT period (HP, 2 years before the index dose of SLIT/SDT [first dispensation]) and four 2-year follow-up periods (FUPs) after the index dose, with the latter 2 periods corresponding to post-treatment years. HCRU was analyzed using a Poisson model with generalized estimating equations. The study population comprised 112 492 SLIT and 333 082 control patients. Dispensations of antihistamines and intranasal corticosteroids decreased by 28% to 49% during the FUPs (IRR from 0.51 [0.50-0.52] to 0.69 [0.67-0.71]) and after treatment (IRR from 0.62 [0.59-0.65] to 0.72 [0.69-0.74]), favoring SLIT-exposed patients. In patients with asthma, a 17%-29% reduction in asthma medication dispensations also favored SLIT-liquid (IRR, 0.83 [0.78-0.88] to 0.71 [0.68-0.74] during treatment; 0.82 [0.77-0.88] to 0.78 [0.72-0.85] after treatment). For oral corticosteroids, the between-group difference in change from the HP was in favor of SLIT-liquid for all FUPs (IRR for doses, 0.66 [0.64-0.69] to 0.79 [0.73-0.85]). The decrease in medical consultations and hospitalizations was consistently more frequent over time in SLIT patients than in controls. In this national real-world study involving the largest number of person-years followed in the field of AIT to date, SLIT-liquid was associated with a reduction in AR and dispensation of asthma medication, including systemic corticosteroids, and medical consultations. The results recorded in the last 2 post-treatment FUPs suggest a sustained effect of SLIT-liquid.

Objective:To explore the efficacy of using drug combination and sublingual immunotherapy（SLIT） for pediatric obstructive sleep apnea（OSA） and allergic rhinitis（AR） after adenotonsillectomy, in order to provide a more optimized treatment plan after the surgery. Methods:A total of 95 pediatric OSA combined with AR were selected. According to the treatment plan, they were divided into the SLIT group（postoperative medication combined with SLIT） and the control group（postoperative medication treatment only）. The comparisons were made between the two groups regarding the scores of the 18-item Quality of Life Questionnaire for Obstructive Sleep Apnea（OSA-18） and the Visual Analogue Scale（VAS） before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment; the monthly total medication scores（TMS） from 1 month to 3 months, 4 months to 6 months, 7 months to 1 year, and 1 year to 2 years after treatment, as well as the number of acute attacks of AR in the 1st year and 2nd year after treatment; and the Lund-Kennedy scores and nasal resistance grading of nasal endoscopy before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment. The effectiveness and safety were also analyzed. Results:After one year of treatment, the OSA-18 score, VAS score, TMS and Lund-Kennedy score in the SLIT group were significantly better than those in the control group. The nasal resistance was significantly reduced（P<0.05）, and the frequency of AR attacks was significantly lower than that in the control group（P<0.05）. After 2 years of treatment, the VAS score, Lund-Kennedy score and nasal resistance classification in the SLIT group tended to stabilize, while the OSA-18 score continued to decline. Conclusion:After surgery for pediatric OSA combined with AR, the use of drugs combined with SLIT can effectively alleviate AR symptoms, further improve OSA-related symptoms and quality of life, reduce drug dependence, decrease the frequency of AR attacks, and enhance the long-term efficacy of the surgery.

This review evaluates the evidence on the effects of allergen immunotherapy (AIT) on lung function in asthma, with a focus on long-term outcomes. The topic is timely given the increasing interest in disease-modifying strategies that may alter asthma's natural course, particularly through interventions targeting type 2 inflammation. Previous long-term observational and randomized studies suggest that sublingual immunotherapy (SLIT) can sustain clinical benefits and may positively impact lung function. However, while improvements in asthma control and exacerbation reduction are consistent, recent and robust evidence for lung function preservation remains limited. Real-world prospective studies from European and Chinese cohorts, point to possible allergen-independent benefits on forced expiratory volume in one second. While AIT is a proven disease-modifying intervention for allergic diseases, its role in preventing or slowing lung function decline in asthma is underexplored. Future research should prioritize longitudinal spirometry data across diverse allergens and patient populations to clarify AIT's potential to alter asthma progression.

BackgroundThe aim of this study is to explore the indicative role of Asthma Control Test (ACT) score in the use of dust mite immunotherapy for asthmatic children by comparing the recovery of lung function in these children who have different ACT scores with or without undergoing dust mite immunotherapy, and to provide a more accurate and applicable method to select the population for dust mite immunotherapy.MethodsA total of 200 children diagnosed with asthma who had tested positive for dust mite allergens from February 2019 to January 2021 were divided into the observation group and control group based on whether sublingual immunotherapy (SLIT) for dust mite allergy was incorporated into their regular asthma treatment. These two groups were further subdivided into ACT > 19 and ACT ≤ 19 groups based on the ACT scores before treatment. After 1 year of follow-up, the lung function and fractional exhaled nitric oxide (FeNO) levels of these four groups were compared before and after treatment.ResultsA total of 160 asthmatic children completed the study. We found that the observation group with ACT > 19 showed better improvement in forced vital capacity (FVC) (z = -2.338 P = 0.019), forced expiratory volume in one second (FEV1) (t = 3.02 P = 0.007), forced expiratory flow at 50% of FVC (FEF50) (t = 2.807 P = 0.012), and forced expiratory flow at 25% of FVC (FEF25) (t = 3.032 P = 0.007) than the control group with ACT > 19. Moreover, the observation group with ACT ≤ 19 showed significantly better improvement in FVC (z = -3.554 P < 0.001), FEV1 (z = -3.71 P < 0.001),forced expiratory flow at 75% of FVC (FEF75) (z = -3.8 P < 0.001), FEF50 (z = -3.733 P < 0.001), FEF25 (z = -5.593 P < 0.001), maximal mid-expiratory flow (MMEF) (z = -3.930 P < 0.001), and FeNO (z = -2.218 P = 0.027) than the control group with ACT ≤ 19. We found that in the observation group, irrespective of whether ACT > 19 or ACT ≤ 19, there was some improvement in all indicators, but there was no significant difference between the two subgroups. In the control group, patients with ACT > 19 showed significantly less improvement in FEV1 and FEF75 than patients with ACT ≤ 19 (z = -2.567 P = 0.010, t = 2.624 P = 0.010, respectively).ConclusionsImmunotherapy for dust mites is effective in improving lung function in children with asthma, especially in those with ACT > 19 before treatment.

This study aimed to investigate the clinical improvement of the incremental dosage regimen in allergic rhinitis (AR) patients with low response to sublingual immunotherapy (SLIT). This retrospective study included 65 AR patients with low response to dust mite SLIT after 6-month treatment. Patients were divided into regular-dose (RD) group (n = 23) and high-dose (HD) group (n = 42). The RD group maintained the previous standard dose, while the HD group received the higher tolerated dose and further categorized into 2 subgroups based on increased doses. Total nasal symptoms score (TNSS), total medication score (TMS), combined symptom and medication score (CSMS), and visual analog scale were compared at baseline, 6 months, and 1 year. Safety was assessed by reported adverse events (AEs).There were no significant differences between RD and HD groups at baseline and 6 months. However, patients in the HD group showed significantly lower TNSS, TMS, CSMS, and visual analog scale at 1 year compared to the RD group (all P <.01). Continued improvements in TNSS, TMS, and CSMS were only found in the HD group from 6-month to 1-year treatment (all P <.01). Moreover, there was no statistical difference between HD subgroups at any follow-up points. In addition, a higher proportion of patients in the HD group discontinued medication. No difference was observed in AEs between RD and HD groups. Dose increment after 6-month SLIT treatment could significantly enhance efficacy in low-response AR patients over a 1-year course without raising the risk of AEs.

Allergic rhinitis (AR) is an IgE-mediated response to aeroallergens. Sublingual immunotherapy (SLIT) alleviates AR by suppressing Th2 responses. This study investigates the mechanism underlying SLIT-mediated Th2 suppression in AR treatment. An AR mouse model was established by intraperitoneal injection of alum-adsorbed Phleum pratense extract in BALB/c mice. SLIT efficacy were assessed by evaluating clinical symptoms, IgE levels, splenic and cervical lymph node (cLN) cell proliferation, cytokine profiles, and proportion of Th17 and Treg cells. Mechanisms were explored using bioinformatics analysis and Western blotting. AR mice displayed increased sneezing, nasal lavage IgE, and eosinophilia. Spleen cell proliferation remained unchanged, while cLN proliferation was elevated. SLIT reversed elevated IL-4/IL-5, Th17, and reduced IFN-γ/Treg levels in both spleen and cLN. Microarray analysis of GSE206149 revealed NFκB pathway enrichment in SLIT-treated AR patients. SLIT inhibited NFκB activation (reduced p-IκBα/p-NFκB p65) in AR mice. The NFκB inhibitor BAY11-7082 amplified SLIT's therapeutic effects, further suppressing Th2 responses. Conversely, IκBα knockdown abolished SLIT's benefits, confirming NFκB's essential role. Collectively, we demonstrated that SLIT inhibits NFκB pathway activation, thereby suppressing the Th2-type immune response and alleviating AR progression. These findings provide new insights into the mechanism of SLIT in the treatment of AR.

Allergy to lipid transfer proteins (LTP) is one of the leading causes of anaphylaxis in the Mediterranean region. Oral immunotherapy, sublingual immunotherapy (SLIT), with peach extract has emerged as a strategy to induce tolerance. This study aimed to evaluate the efficacy of SLIT with peach extract and the usefulness of serological biomarkers as predictors of clinical response in patients with LTP-related anaphylaxis. Observational study involving 80 patients diagnosed with LTP syndrome. Total IgE levels, specific IgE, and IgG4 specific to Pru p 3 were measured before and after 1 year of treatment. Patients were classified based on tolerance at the end of therapy. Sixty-one patients (76.3%) tolerated the final oral challenge. Baseline levels of total IgE, specific IgE, and IgG4 specific to Pru p 3 were significantly higher in the tolerance group. IgG4 levels increased significantly in both groups after treatment. Specific IgE levels increased only in the nontolerance group. SLIT with peach extract may induce tolerance in the majority of patients with LTP allergy. Elevated baseline levels of total IgE, specific IgE, and IgG4 specific to Pru p 3 could serve as markers of clinical response.

Dendritic cells are specialized antigen presenting cells that bridge innate and adaptive immune responses. Here, we focus on the role of dendritic cells in food tolerance and food allergy pathogenesis and treatment. In addition to dendritic cells, the recently identified subset of RORγt+ antigen presenting cells appears to contribute to oral tolerance to foods. Dendritic cells play a central role in establishing oral food tolerance, but also in aberrantly promoting allergic sensitization when activated by certain inflammatory environmental stimuli. We review what is known about the environmental signals, dendritic cell subsets, and dendritic cell responses that promote both oral food tolerance and allergic sensitization. We also discuss the role of dendritic cells in emerging food allergy treatments such as oral immunotherapy and sublingual immunotherapy. Dendritic cells thus play important and multifaceted roles in tolerance and allergy to foods, and better mechanistic understanding of what distinguishes these processes could lead to improved food allergy prevention and treatment strategies.

The safety and efficacy of 36-month peanut sublingual immunotherapy (SLIT) was recently demonstrated in peanut-allergic children (1-4 years old), with high remission rates three months post-treatment. We performed a post hoc analysis of longitudinal changes in peanut component-specific IgE (PnC-sIgE) and IgG4 (PnC-sIgG4) levels in 1-4 year olds who underwent peanut SLIT to uncover immune mechanisms and potential biomarkers of remission. Plasma from 30 participants was analyzed at 0, 12, 24, 36, and 39 months using ImmunoCAP250 for PnC-sIgE and PnC-sIgG4 to Ara h 1, Ara h 2, Ara h 3, and Ara h 6 (Ah1-6). Mixed-effects models assessed longitudinal antibody changes, Wilcoxon tests compared antibody levels by remission status, and correlations evaluated age and baseline antibody levels. Peanut SLIT reduced IgE levels while increasing IgG4 levels specific to Pn and Ah1-6 over 36 months. No changes in sIgE were observed in the placebo group, whereas increases in Pn-, Ah1-, and Ah3-sIgG4 were noted. Participants achieving remission had lower IgE and IgG4 to Pn and Ah1-6 at baseline and throughout 36 months of SLIT. Ah2-sIgG4 showed no overlap between outcome groups at baseline, suggesting potential as a biomarker. Children under 3 had lower baseline Ah6-sIgE and Ah1-, Ah2-, and Ah6-sIgG4 levels and higher remission rates than those 3 and older, linking age, remission, and antibody profiles. Component-resolved analysis offers key insights into the immunological mechanisms in young children undergoing peanut SLIT, revealing lower baseline levels of Ah2-sIgG4 as a potential biomarker of remission.