Subcutaneous Immunotherapy Group Research Articles

Effectiveness of allergen immunotherapy with house dust mite extract for pediatric bronchial asthma.

Aim: We compared the effectiveness of rush subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) using standardized house dust mite (HDM) extract for pediatric bronchial asthma (BA). Methods: We followed the pediatric BA treatment score during 3 years of treatment. We assessed the median time to no longer requiring long-term control pharmacotherapy (LTCP) for BA (LTCP-free). We compared the outcomes after adjustment for confounding factors and propensity score matching. Results: Patients in the HDM SCIT group achieved the LTCP-free status significantly earlier than those in the HDM SLIT group after adjustment for confounding factors and propensity score matching. Conclusion: Patients treated for pediatric BA with rush HDM SCIT had earlier onset of therapeutic effects than those with HDM SLIT.

Comparison of the therapeutic effects of medication therapy, specific immunotherapy and anti-IgE (Omalizumab) in patients with hay fever.

Hay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents, and specific immunotherapy. This study aims to assess and compare the effectiveness of anti-IgE (omalizumab), medication therapy, and subcutaneous immunotherapy (SCIT) for hay fever. Conducted as a retrospective cohort study, this research involved 98 outpatient hay fever patients who underwent routine medication, omalizumab treatment, or SCIT before the onset of the spring pollen season. A follow-up was performed one month after the start of the pollen season. The comprehensive symptoms and drug scores were used to evaluate patients with different intervention methods, facilitating a comparative analysis of therapeutic outcomes. Compared with before treatment, the symptoms of patients treated with the three methods were all significantly relieved, and the medication score were significantly reduced. Patients treated with omalizumab demonstrated higher symptoms and medication scores than SCIT group before treatment, but similar scores after treatment, which were both lower than medicine treatment group. After treatment with omalizumab or SCIT, patients in both groups had significantly lower medication scores than the medication group and were close to no longer using medication for symptom relief. The mountain juniper-sIgE was significantly higher after treatment than before treatment in both medicine treatment group and omalizumab treatment group. Omalizumab and SCIT offer superior effects than medication therapy in hay fever patients.

The long-term efficacy of intra-cervical lymphatic immunotherapy on adults with allergic rhinitis: A randomized controlled study.

The efficacy and safety of the novel immunotherapy method, intra-cervical lymphatic immunotherapy (ICLIT), need to be investigated. Comparing it with subcutaneous immunotherapy (SCIT), we clarified the long-term efficacy and safety of intra-cervical lymphatic immunotherapy on allergic rhinitis (AR), and investigated the improvement of clinical efficacy of the booster injection at 1year after ICLIT treatment. Ninety adult patients with dust mite allergy were randomly divided into 3 groups: 30 in the SCIT group, 30 in the ILCLIT group, and 30 in ICLIT booster group. Changes in total symptom score (TSS), nasal symptom score (TNSS), ocular symptom score (TOSS) and total medication score (TMS) were evaluated in the three groups. Adverse reactions were recorded, and serum dust mite specific IgE (sIgE) and specific IgG4 were assessed in the ICLIT group and ICLIT booster group. TSS, TNSS, TOSS, and TMS scores were significantly lower in the three groups at 36months after treatment (p<0. 05). And at 36months the ICLIT-booster group showed results similar to SCIT and superior to ICLIT (p<0. 05). Serum specific IgE decreased in all three groups at 12 and 36months after treatment, p<0.01. The ICLIT group and the ICLIT booster group showed a significant increase in sIgG4, p<0.01. None of the patients in the three groups had any serious systemic adverse effects during the 3-year follow-up. The ICLIT treatment is effective and safe on AR. One booster injection of allergens at 1year can greatly improve its long-term efficacy. Clinical trial registration number: ChiCTR1800017130.

Sublingual versus subcutaneous allergen immunotherapy in bronchial asthma: A randomized controlled trial

Abstract Background Asthma affects 300 million individuals worldwide. It is a serious global health problem affecting all age groups. The significance of eosinophilic inflammation in asthma is well established. Allergen immunotherapy (AIT) acts by increasing tolerance to specific antigens to which individuals demonstrate clinical sensitivity. Objectives Evaluate the efficacy and safety of sublingual immunotherapy (SLIT) versus subcutaneous immunotherapy (SCIT) as regards clinical response, total immunoglobulin E (IgE), and sputum eosinophil as well as adverse effects. Methods This randomized clinical trial included 100 patients with bronchial asthma who were randomly allocated into two groups: the SLIT group (n = 50) and the SCIT group (n = 50). Patients were given a full allergy history, symptoms, and medication scores; a skin prick test; total IgE for allergens, and a sputum eosinophil count. After the end of treatment, the efficacy, as well as side effects of both treatment arms, were evaluated at 6, 12, and 18 months. Results Both SLIT and SCIT were equally effective. Success rates have been demonstrated to be as high as 86–88%. There was a statistically significant decrease in symptom and medication scores, Total IgE levels, and sputum eosinophil results after treatment (P &lt; 0.001). However, no difference was found between groups regarding the efficacy of treatment. SLIT was significantly safer than SCIT (P &lt; 0.001). Conclusion Both treatment modalities were equally effective in treating asthma, but SLIT had a higher safety profile than SCIT.

Efficacy and safety of sublingual versus subcutaneous immunotherapy in children with allergic rhinitis: a systematic review and meta-analysis.

To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR). PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison. Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, P = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, P = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26). Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians. PROSPERO (CRD42023460693).

Comparison of rush-subcutaneous and sublingual immunotherapy with house dust mite extract for pediatric allergic rhinitis: A prospective cohort study

BackgroundWe aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for allergic rhinitis. MethodsParticipants with allergic rhinitis selected their treatment between HDM SCIT or HDM SLIT, according to their wishes. We prospectively followed symptoms of allergic rhinitis using the allergic rhinitis symptom medication score (ARSMS), along with adverse reactions, during the dose escalation and maintenance phases for two years. We compared the outcomes between propensity score-matched groups to adjust the confounding factors. ResultsAfter propensity score matching, 88 patients in the HDM SCIT (n = 44) and HDM SLIT groups (n = 44) remained for analysis. The HDM SCIT group showed significantly earlier effectiveness than the HDM SLIT group (median time to decrease in ARSMS [≥2 points]: 5.5 vs. 18.0 months, p < 0.001). The incidence of systemic reactions was not significantly different between the two groups in the dose escalation phase (68.2% vs. 56.8%, p = 0.379). In the maintenance phase, the incidence of systemic reactions was higher in the HDM SCIT group than in the HDM SLIT group (18.2% vs. 0%, p < 0.006). All 44 patients in the HDM SCIT group completed two years of treatment, while nine patients in the HDM SLIT group discontinued treatment. ConclusionsThe HDM SCIT group showed an earlier onset of therapeutic effect and a lower discontinuation rate than the HDM SLIT group, although more severe systemic reactions were observed during the maintenance phase.

Can development of asthma and bronchial hyperreactivity be reduced by subcutaneous immunotherapy in adult patients with allergic rhinitis?

Allergic rhinitis can be associated with bronchial hyperreactivity (BHR) and create an increased risk for allergic asthma development. We aimed to investigate the effects of subcutaneous immunotherapy (SCIT) on BHR and asthma development in adult patients with allergic rhinitis. The retrospective case-control study was carried out between November 2018 and May 2019 in Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital. In this study, data was recorded for patients with a mite and/or grasses/cereals pollen allergy who were tested for BHR before planned SCIT, and who had allergic rhinitis, with or without asthma. The SCIT group was selected as those who received SCIT for at least one year. The control group was selected from those who were scheduled to receive SCIT but were waived and still receiving medication. Symptom scores, prick test results, PC20 levels (methacholine challenge that is a provocative concentration causing a 20% fall in FEV1), and the presence of asthma were recorded and compared with data from at least one year after treatment. A total of sixty-eight subjects (22 males, 46 females; mean age 40.54 ± 12.27 years; SCIT: 40, Control: 28) were enrolled.Although the changes in log PC20 levels were not statistically significant in both SCIT and control groups after an average of 30-35 months of treatment, it was found to be significant in favor of the SCIT group when two groups were compared in terms of the change in log PC20 (p = 0.026). The development and improvement of asthma were not significantly different between the SCIT and control group but tended to increase in the control group. The percentage of patients with progressed/BHR was significantly higher in the controls (70.6% vs. 38.1%, p = 0.046). In our real life study we have demonstrated the preventative effect of SCIT on BHR, but not on asthma developmen.

Safety Profile and Issues of Subcutaneous Immunotherapy in the Treatment of Children with Allergic Rhinitis.

This study aims to evaluate safety issues of house dust mite subcutaneous immunotherapy (SCIT) among allergic rhinitis (AR) children. A retrospective cohort study was done between 2015 and 2020 to investigate the side effects of SCIT among AR children caused by a house dust mite allergy. Among 1098 patients who received house dust mite subcutaneous immunotherapy injections, 284 patients (25.87%) had side effects (SE). SE were found to be 699 times higher or in 2.27% of the 30,744 subcutaneous immunotherapy injections. A total of 17.9% of the patients had local SE during SCIT administration. Systemic side effects occurred in 8.38% of children receiving SCIT and in 0.53% of the total population who received SCIT injections. Only 2/92 (2.18%) of patients suffered an allergic reaction within 30 minutes of injection and these patients responded well to antiallergic medication. Severe anaphylaxis occurred in 0.091% of the 1098 patients in the SCIT group and in 0.0033% of the 30,774 SCIT injections. Systemic SE after SCIT occurred in 8.38% of patients receiving SCIT or 0.53% of the total number of SCIT injections. Anaphylactic episodes occurred in 16 patients (1.46%) and 15 patients (1.37%) who had first and second episodes. One severe attack was found and it was resolved with adrenaline. This study demonstrates that in pediatric patients with AR who received HDM SCIT for 18 months with high adherence, some experienced significant local SE and systemic SE caused by SCIT, but this did not interfere with the course of AR treatment or the effectiveness of SCIT.

A Randomized Trial of Subcutaneous Allergy Immunotherapy in Inner-city Children With Asthma Less Than 4 Years of Age

To evaluate the effect of subcutaneous immunotherapy (SCIT) on asthma in inner-city children <4 years of age.Children between the ages of 18 to 47 months were recruited when seen in the asthma or allergy clinic at Jacobi Medical Center in Bronx, New York, which cares for a mostly low-income, inner-city population. Participants were required to have physician-diagnosed asthma or at least 2 lifetime episodes of wheezing and be at high risk of persistent asthma on the basis of an Asthma Predictive Index. Patients with any other chronic medical condition, history of severe prematurity, or a sustained oxygen requirement at birth were excluded. Although all patients had at least 1 common environmental allergen positive on skin-prick testing, most had multiple and mainly indoor allergen sensitizations. The majority of patients were male and used an asthma controller medication, with an average asthma symptom score indicating mild persistent asthma.Participants were randomly assigned to the SCIT (n = 27) or control group (n = 23). SCIT was administered per published guidelines, with biweekly maintenance injections. Asthma, nasal-ocular, and skin symptom scores and medication use were monitored by a phone call every 2 weeks. In interim power analysis, it was indicated there was an insufficient sample size to reach the planned power of 80%, so the study was terminated early before some participants had completed SCIT for 3 years.On the basis of intention-to-treat analysis, there was no statically significant difference in asthma, nasal-ocular, or skin symptom scores in the SCIT and control groups. Quality of life, as assessed by the parent, showed significant improvement in the SCIT group (β coefficient: 0.32; SE: 0.09; P ≤ .01), particularly related to interference of child’s asthma on family or work plans and nighttime symptoms. Allergen specific serum immunoglobulin G4 levels increased in the SCIT group only (P ≤ .04). New allergen sensitization or loss of sensitization rates at the end of the study were not significantly different between the SCIT and control groups. Systemic reactions occurred in in 22% of children and 1.8% of injections, all of which were mild and resolved with antihistamine administration. Children in the SCIT group missed 28% of injection visits.Apart from improved quality of life, allergen immunotherapy in inner-city children with asthma <4 years of age did not show significant improvement in asthma, allergy, or eczema clinical outcomes.Although perhaps limited by small sample size and a high rate of missed appointments, with the results, the authors support the common practice of waiting until near 5 years of age to start SCIT. Factors unique to an inner-city, younger pediatric population may warrant larger studies to determine the efficacy of early immunotherapy in improving asthma.

Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial.

BackgroundSubcutaneous immunotherapy (SCIT) has been proven as an effective therapy against some allergens for seasonal allergic rhinitis (SAR) patients unresponsive to intranasal corticosteroids and/or antihistamines but carries risk of systemic allergic reactions. Dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation in multiple diseases.ObjectiveTo evaluate the efficacy and safety of SCIT+dupilumab vs SCIT alone.MethodsThis phase 2a, multicenter, double-blind, placebo-controlled parallel-group study conducted in 103 adults with grass pollen-induced SAR (NCT03558997) randomized patients 1:1:1:1 to SCIT, dupilumab (300 mg every 2 weeks), SCIT+dupilumab, or placebo. SCIT was administered using an 8-week cluster protocol followed by 8 weeks of maintenance injections. Primary endpoint was change from pre-treatment baseline in area under the curve (AUC) in total nasal symptom score (TNSS) 0–1 h following nasal allergen challenge (NAC) with timothy grass extract at Week 17.ResultsAlthough 16 weeks of treatment with SCIT+dupilumab did not significantly improve TNSS AUC (0–1 h) following NAC at Week 17 vs SCIT (least squares mean −56.76% vs −52.03%), a higher proportion of SCIT+dupilumab-treated patients (61.5%) achieved SCIT maintenance dose vs SCIT (46.2%). A lower proportion of SCIT+dupilumab-treated patients (7.7%) required epinephrine rescue treatment vs SCIT (19.2%). There were significantly fewer withdrawals in the SCIT+dupilumab group than in the SCIT group (n = 2 [7.7%] vs n = 8 [30.8%]; P = 0.0216); the majority of SCIT group withdrawals were due to SCIT-related intolerability, compared with no discontinuations from the SCIT+dupilumab group.ConclusionIn SAR patients, 16 weeks of SCIT+dupilumab may improve SCIT tolerability but did not incrementally reduce post-allergen challenge nasal symptoms compared with SCIT alone.Clinical Study NumberNCT03558997.

Analysis of the long-term efficacy and safety of subcutaneous immunotherapy for atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Subcutaneous immunotherapy (SCIT) refers to repeated contact with gradually increasing doses of allergen extracts, which improve patient tolerance to such allergens and controls, or reduces allergic symptoms. This study aimed to explore the long-term efficacy and safety of SCIT for patients with AD sensitized to house-dust mite (HDM). Methods: We conducted a retrospective analysis of 378 patients with HDM-sensitized AD. Among these patients, 164 received SCIT plus pharmacotherapy for 3 years (SCIT group) and the other 214 patients received only pharmacotherapy (non-SCIT group). The scoring atopic dermatitis (SCORAD) and pruritus visual analog scale (VAS) scores, laboratory test results, and adverse effects were recorded. Results: The SCORAD and pruritus VAS scores significantly decreased in the SCIT group. Also, the SCIT group showed higher reduction ratios of SCORAD and pruritus VAS scores than those observed in the non-SCIT group at 3 years after treatment initiation. The risk of development of new sensitization was higher in the non-SCIT group than in the SCIT group (relative risk 1.92 [95% confidence interval {CI}, 1.30-2.85]; p < 0.05). The eosinophil count of the participants significantly differed in the complete response (CR) group (p < 0.05) but not in the non-CR group (p = 0.098). However, the serum total immunoglobulin E value was not significantly reduced (p = 0.204). Of 8421 injections given to the patients, 231 injections (2.74%) showed adverse effects during the treatment period. Conclusion: Three years of SCIT can significantly reduce the severity and pruritus of moderate-to-severe AD with HDM sensitization. Patients who are multisensitized can also benefit from HDM SCIT. Patients can achieve long-term effects, such as prevention of neoallergen sensitization and inhibition of the allergy march.

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

Allergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance. We sought to evaluate the role of circulating CXCR5+PD-1+ T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) and the accompanying changes in their chromatin landscape. Phenotype and function of cTFH cells were initially evaluated in the grass pollen-allergic (GPA) group (n= 28) and nonatopic healthy controls (NAC, n= 13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n= 12), GPA (n= 14), SCIT- (n= 10), and SLIT- (n= 8) treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by assay for transposase-accessible chromatin sequencing (ATAC-seq) to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT, and SLIT groups. cTFH cells were shown to be distinct from TH2- and TH2A-cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B-cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH-cell proliferation in the GPA group but not in the NAC group (P< .05). cTFH cells were higher in the GPA group compared with the NAC group and were lower in the SCIT and SLIT groups (P< .01). Time-dependent induction of IL-4, IL-21, and IL-6 was observed in nasal mucosa following intranasal allergen challenge in the GPA group but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT groups (all, P< .01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups. For the first time, we showed dysregulation of cTFH cells in the GPA group compared to NAC, SCIT, and SLIT groups and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following allergen-specific immunotherapy in cTFH and TFR cells.

Efficacy, safety and compliance of immunotherapy in the treatment of allergic rhinitis: a Meta-analysis

Objective: By use of Meta analysis to compare efficacy, safety and compliance of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) on allergic rhinitis (AR). Methods: Cochrane Library, Pubmed, Embase, CNKI Database, Wan Fang and Chinese Sci-tech Journal Database (from established time to May of 2018) were searched for trials about the AR treated by SCIT and SLIT. The relevant literatures were screened, and the randomized controlled studies were chosen. Nasal symptom scores, visual analogue scale (VAS) scores, adverse reactions and compliance were used as the outcome indicators, and the methodological quality of the literatures was evaluated strictly. The extracted data were analyzed by RevMan 5.3 and Stata 14 software. Results: A total of 20 randomized controlled studies were included, the overall quality of which was relatively high. No publication bias was found. There was no significant difference in nasal symptom scores, VAS scores and compliance between SCIT and SLIT (SMD value was 0.03, 0.14, respectively, RR=1.12; 95%CI value was -0.17-0.23, -0.03-0.31, 0.92-1.35, respectively, all P>0.05); SLIT group resulted in lower overall incidence of adverse reactions than that of SCIT group (RR=1.79, 95%CI: 1.42-2.26, P<0.05). Conclusion: Both SCIT and SLIT have similar eppecacy and compliance for treatment of AR, while adverse reactions are more frequently observed in SCIT.

Immunoregulatory Effects of Subcutaneous Immunotherapy on Lymphocyte Subgroups and Cytokines in Children with Asthma.

Objective Asthma is a syndrome that incorporates many immune phenotypes. The immunologic effects of subcutaneous immunotherapy (SCIT) exerts on allergic asthma remain still largely unknown. Here, we investigated the effects of SCIT on cytokine production and peripheral blood levels of lymphocyte subtypes in children with mite-induced moderate and severe allergic asthma. Methods The study included 60 kids with mite-induced allergic asthma from 5 to 10 years old. All subjects had received antiasthmatic pharmacologic for 3 months at baseline. Half of the children were treated with SCIT combined with pharmacologic treatment named the SCIT group and the other half only with pharmacologic therapy named the no-SCIT group. Total asthma symptom score (TASS) and total medication score (TMS) were recorded. Flow cytometry was used to identify lymphocyte subtypes: type 2 innate lymphocytes (ILC2s), type 1 (Th1) and type 2 (Th2) helper T cells, T helper 17 (Th17) cells, and regulatory T (Treg) cells. ELISA, flow cytometry, and cytometric bead array were used to assess cytokines IL-13, IFN-γ, IL-4, IL-17, and TGF-β, at baseline and 3 and 6 months after study treatment in both groups of patients. Results Both groups can significantly improve clinical symptoms in children with asthma. SCIT can significantly reduce asthma medication after 6 months of treatment. SCIT induced a significantly higher and progressive reduction in ILC2 percentage and IL-13 levels after 3 and 6 months of treatment compared with baseline and compared with no-SCIT patients. Significant differences were detected in the Th1/Th2 cell ratio and IFN-γ/IL-4 cytokine ratio between groups after 6 months of treatment. Similarly, the Th17/Treg ratio and IL-17/TGF-β ratio in the SCIT group were much lower than those in the no-SCIT group after 3-6 months of treatment. Conclusion SCIT is a promising option to reduce the percentage of ILC2 and regulate Th1/Th2 and Th17/Treg immune balance in the peripheral blood of children with asthma.

Establishment of enzyme-linked immunosorbent facilitated antigen binding as a biomarker assay for Japanese cedar pollen allergy immunotherapy

BackgroundClinical efficacy of allergen-specific Immunotherapy (AIT) towards Japanese cedar (JC) pollen allergy is firmly established but JC pollen-specific biomarker assays are lacking. Treatment-related increase of allergen-specific antibodies is a robust biomarker of successful AIT. Allergen-specific non-IgE antibodies are believed to reduce the effects of allergen exposure by competing with IgE for allergen binding, and in-vitro assays quantifying the effects of AIT-induced IgE-blocking antibodies are advantageous. A cell-free enzyme-linked immunosorbent facilitated antigen binding (ELIFAB) assay of JC pollen was established. MethodsSerum IgE–allergen complexes were captured by immobilized recombinant CD23, and allergen–IgE–CD23 complexes were detected by a biotin-conjugated anti-human IgE antibody. Sera from JC pollen-allergic subjects without or with subcutaneous immunotherapy (SCIT) with JC pollen extract were used (n = 11/group). ResultsOptimal assay conditions were established at 20 μg/mL CD23 and 0.3 μg/mL JC pollen extract, and the dependency on CD23 and IgE was verified. The data show that the JC pollen ELIFAB assay is fit for purpose and demonstrates that the IgE-blocking activity is significantly increased in the JC pollen SCIT group compared with the non-treated group. ConclusionThe JC pollen ELIFAB assay represents a simple, cell-free biomarker assay for monitoring the development of IgE-blocking antibody activity during JC pollen AIT.

Epigenetic Modification of Enhancer of Zeste Homolog 2 Modulates the Activation of Dendritic Cells in Allergen Immunotherapy

Background: Allergen immunotherapy (AIT) is the only etiological and potentially curative therapy for allergic rhinitis (AR). Objectives: We sought to investigate the role of epigenetic regulator enhancer of zeste homolog 2 (EZH2) in the activation of dendritic cells (DCs) in AIT. Method: In this study, EZH2 expression in circulating myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were evaluated using flow cytometry. Clinical information from 56 AR patients receiving AIT was collected, including 30 subjects with subcutaneous immunotherapy (SCIT) and 26 subjects with sublingual immunotherapy (SLIT). In vitro, the effect of EZH2 inhibitor, 3 Deazaneplanocin A (DZNep), on the phenotypic and functional activation of monocyte-derived DCs (moDCs) was evaluated. Results: EZH2 expression in circulating mDCs and pDCs were both negatively correlated to treatment time of AIT (r = –0.39, p = 0.003 and r = –0.47, p = 0.0002, respectively). Furthermore, there was a higher correlation between EZH2 expression and AIT treatment time in the SCIT group compared to that of the SLIT group in mDCs (r = –0.42, p = 0.02 vs. r = –0.23, p = 0.26)and pDCs (r = –0.52, p = 0.003 vs. r = –0.33, p = 0.10). In vitro, the co-stimulatory molecules on moDCs, such as CD80, CD86, and CD83, were significantly inhibited by DZNep in a dose-dependent manner. The ­DC-driven T-cell proliferation was suppressed by DZNep (MD = 22.88, 95% CI 7.809–37.96, p < 0.05). Conclusions: Our study shows that EZH2, which is required in the activation of DCs, mediates the epigenetic modification in AIT and stresses the importance of patient adherence during AIT.

Systemic reaction rates with omalizumab, subcutaneous immunotherapy, and combination therapy in children with allergic asthma.

Background: For children with moderate-to-severe persistent allergic asthma, omalizumab is effective. However, it is expensive, and there are no current guidelines for discontinuation. Subcutaneous immunotherapy (SCIT) is the only approach that can provide persistent beneficial effects after treatment is discontinued. However, SCIT is contraindicated in poorly controlled asthma. Therefore, we performed, to our knowledge, the first U.S. study that exclusively compared the safety of omalizumab, SCIT, and combination (omalizumab and SCIT) therapy in children with allergic asthma. Objective: We hypothesize that the systemic reaction (SR) rates in children who receive combination therapy are comparable with omalizumab alone. Methods: We performed a retrospective study of children ages 6-18 years old with allergic asthma who, from July 2010 to June 2017, received SCIT, omalizumab, or combination therapy in our children's allergy clinic. Our primary end point was to determine the SR rate among each of these groups. Results: We reviewed the records of 89 patients: 30 patients with SCIT (1550 injections), 30 patients with omalizumab (729 injections), and 29 patients with combination therapy (954 injections). In the SCIT group, 19 SRs (1.2% of injections) occurred in 10 patients (33%). In the omalizumab group, three SRs (0.4% of injections) occurred in three patients (10%). Similarly, in the combination group, three SRs (0.3% of injections) occurred in three patients (10%). Compared with the SR rate in the SCIT group, both omalizumab and combination groups had significantly lower SR rates (p = 0.045 and p = 0.011, respectively). The SR rates in children who received omalizumab and children who received combination therapy were not statistically different (p = 0.73). Conclusion: Children with moderate-severe persistent allergic asthma who received omalizumab or combination therapy had significantly lower SR rates compared with children with allergic asthma who received SCIT alone. SCIT in children treated with omalizumab was safe and may serve both as an omalizumab-sparing treatment and as a bridge to safely administer SCIT.

Nasal allergen-neutralizing IgG4 antibodies block IgE-mediated responses: Novel biomarker of subcutaneous grass pollen immunotherapy

Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG4-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells. We sought to determine whether SCIT induces nasal allergen-specific IgG4 antibodies with inhibitory activity that correlates closely with clinical response. In a cross-sectional controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergic patients (with seasonal allergic rhinitis [SAR]), and 12 nonatopic control subjects. Nasal and serum IgE and IgG4 levels to Phleum pratense components were measured by using the Immuno Solid Allergen Chip microarray. Inhibitory activity was measured by IgE-facilitated allergen binding assay. IL-10+ regulatory B cells were quantified in peripheral blood by using flow cytometry. Nasal and serum Phl p 1- and Phl p 5-specific IgE levels were increased in patients with SAR compared to nonatopic control subjects (all, P<.001) and SCIT-treated patients (nasal, P < .001; serum Phl p 5, P = .073). Nasal IgG4 levels were increased in the SCIT group compared to those in the SAR group (P<.001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in the SCIT group compared to that in the SAR (both, P<.01). The magnitude of the inhibitory activity was 93% (P < .001) in nasal fluid compared to 66% (P < .001) in serum and was reversed after depletion of IgG. Both nasal fluid (r=-0.69, P=.0005) and serum (r=-0.552, P=.0095) blocking activity correlated with global symptom improvement. IL-10+ regulatory B cells were increased in season compared to out of season in the SCIT group (P<.01). For the first time, we show that nasal IgG4-associated inhibitory activity correlates closely with the clinical response to allergen immunotherapy in patients with allergic rhinitis with or without asthma.

Quality-of-life outcomes in patients who underwent subcutaneous immunotherapy and sublingual immunotherapy in a real-world clinical setting.

To compare changes in quality of life (QOL) that resulted from sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) in a real-world clinical setting. SLIT is established as a viable alternative to SCIT for the treatment of allergic rhinitis. Although comparative trials are increasingly available, few studies have examined QOL outcomes between these two treatments. One hundred and five participants who underwent immunotherapy for airborne allergies were enrolled in this prospective, single-center study. Forty participants completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation of therapy, after 6 months, and after 1 year of therapy. Only patients with complete time points were included in the ultimate analysis. Twenty-nine of these participants underwent SCIT and 11 underwent SLIT. The effects of age, sex, and asthma history were also examined. The participants in both groups demonstrated improvements in QOL regarding allergic rhinoconjunctivitis over the study period. However, the change in the RQLQ score from both baseline to 6 months and baseline to 1 year was only statistically significant in the SCIT group (p = 0.002, 6 months and 1 year). The participants in the SCIT group also demonstrated statistically significant improvement from baseline to 1 year in the specific domains of practical and emotional functioning, nasal symptoms, non-nasal/eye symptoms, and sleep. After 1 year, both SCIT and SLIT demonstrated a minimally important difference from baseline in the overall RQLQ score. Age <35 years in the SCIT group had a significant positive impact on QOL improvement (p = 0.038). Although improvements in QOL were noted in both groups, changes in overall scores and the majority of domains only achieved statistical significance in the SCIT group. A small study population and difficulties adhering to immunotherapy dosing schedules in the SLIT group may be contributing factors.

Single-allergen sublingual immunotherapy versus multi-allergen subcutaneous immunotherapy for children with allergic rhinitis.

It has always been controversial whether a single allergen performs better than multiple allergens in polysensitized patients during the allergen-specific immunotherapy. This study aimed to examine the clinical efficacy of single-allergen sublingual immunotherapy (SLIT) versus multi-allergen subcutaneous immunotherapy (SCIT) and to discover the change of the biomarker IL-4 after 1-year immunotherapy in polysensitized children aged 6-13 years with allergic rhinitis (AR) induced by house dust mites (HDMs). The AR polysensitized children (n=78) were randomly divided into two groups: SLIT group and SCIT group. Patients in the SLIT group sublingually received a single HDM extract and those in the SCIT group were subcutaneously given multiple-allergen extracts (HDM in combination with other clinically relevant allergen extracts). Before and 1 year after the allergen-specific immunotherapy (ASIT), the total nasal symptom scores (TNSS), total medication scores (TMS) and IL-4 levels in peripheral blood mononuclear cells (PBMCs) were compared respectively between the two groups. The results showed that the TNSS were greatly improved, and the TMS and IL-4 levels were significantly decreased after 1-year ASIT in both groups (SLIT group: P<0.001; SCIT group: P<0.001). There were no significant differences in any outcome measures between the two groups (for TNSS: P>0.05; for TMS: P>0.05; for IL-4 levels: P>0.05). It was concluded that the clinical efficacy of single-allergen SLIT is comparable with that of multi-allergen SCIT in 6-13-year-old children with HDM-induced AR.