Cluster Immunotherapy Research Articles

Diagnosis and treatment of Hymenoptera venom allergy in adults: A single-center experience in Lithuania

BackgroundVenom-specific immunotherapy (VIT) is a major treatment for patients allergic to Hymenoptera venom. Thus, correct diagnosis of sensitization, identification of the risk factors, and choice of venom for the treatment are the key issues. ObjectiveWe aimed to describe diagnostic and treatment experience data of VIT performed in a single center in Lithuania. MethodsIn this retrospective study, we analyzed 9 years of clinical data (severity of the allergic reaction, recognition of the culprit insects, diagnostics, VIT protocol safety and efficacy, sting challenge outcomes) of patients treated with cluster VIT. Sting challenge helped to reveal the influence of venom preparation quality and to adjust the dosage of venom. ResultsData from 83 patients were analyzed. Double sensitization confirmed by component diagnosis was found in 39.4% (13/33), and double immunotherapy was initiated in 9.1% (n = 3/33). The cluster immunotherapy protocol was used in 81 patients. Systemic reactions occurred in 7.4% (n = 6/81) patients during the build-up phase. VIT failure was related to bee venom immunotherapy and systemic reactions during a build-up phase. The efficacy in the short term of our approach to cluster VIT was confirmed by the sting challenge in 97% (42/43). Nine patients (10.8%, n = 9/83) voluntarily stopped the treatment due to a lack of motivation. ConclusionOur protocol regarding the investigation and treatment of patients allergic to Hymenoptera venom has been safe and effective. Patient's motivation to continue VIT is one of the concerns, but the biggest challenge is the patients with bee venom allergy and repeated systemic reactions during VIT.

Short-term efficacy and safety observation of standardized mite allergen extract rush subcutaneous immunotherapy for allergic rhinitis: a prospective study

Objective: To conduct a comparative analysis of the efficacy, safety, and cytokine changes associated with three distinct dose escalation regimens of allergen-specific immunotherapy (AIT), and to provide valuable insights into the implementation of safer and more effective accelerated immunotherapy in clinical practice. Methods: A prospective study of subcutaneous immunotherapy (SCIT) was conducted at Renmin Hospital of Wuhan University, involving patients with allergic rhinitis visited from 2019 to 2022. Participants were allocated to one of three treatment groups based on their preferences: conventional immunotherapy (CIT, 23 cases), cluster immunotherapy (CLIT, 25 cases), or rush immunotherapy (RIT, 18 cases). The RIT group received a single subcutaneous injection of 150 mg of omalizumab one week before commencing treatment. Subjective evaluation indices, including the Combined Symptom and Medication Score (CSMS), Visual Analogue Scale (VAS), and single symptom score, were recorded alongside objective evaluation indices (e.g., sIgE, tIgE, Th1/2 and Th17 cytokines) and adverse reactions. Assessments were conducted at baseline, and at 1, 7, and 15 weeks after treatment. SPSS 22.0 software was used for data processing and analysis. Results: The study included a total of 66 patients, comprising 37 males and 29 females, who completed the treatment regimen. In all three groups, CSMS and VAS scores showed significant reductions at 1, 7, and 15 weeks post-treatment (all P<0.05). Notably, the RIT group demonstrated a significantly lower VAS score (4.33±0.94) compared to the CIT (9.48±1.37) and CLIT (9.44±1.33) groups at 1 week post-treatment (P<0.05). Additionally, the RIT group (0.62±0.23) exhibited a lower CSMS score than the CIT (1.54±0.21) and CLIT (1.06±0.22) groups at 15 weeks post-treatment (P<0.05). Furthermore, at the point of reaching the maintenance dose, the RIT group (0.61±0.20) demonstrated superior improvement in nasal itching symptoms compared to the CIT (1.78±0.38) and CLIT groups (1.56±0.32), with P<0.05. The incidence of local adverse reactions in the RIT group (36/11.76%) was lower than that in the CIT (69/20.00%) and CLIT groups (62/16.53%), with P<0.05. Notably, none of the three groups reported grade 3/4 systemic adverse reactions, and there was no statistically significant difference in systemic adverse reactions among the three groups. Following treatment, IL-4, IL-5, IL-6, IL-17, sIgE, sIgE/tIgE, and Eos% exhibited varying degrees of decrease in all three groups, whereas IL-10, TNF, and IFN-γ did not show significant changes. Conclusions: All three distinct dose escalation regimens of SCIT demonstrated substantial clinical efficacy. Of note, the approach of combining a single injection of omalizumab with RIT significantly improved early-stage efficacy and exhibited the advantages of safety, effectiveness, and convenience, establishing it as a reliable immunotherapy method.

The early-phase transcriptome and the clinical efficacy analysis in three modes of subcutaneous immunotherapy for allergic rhinitis

BackgroundAllergen immunotherapy is the only etiological treatment for allergic rhinitis. ObjectiveTo analyze the efficacy, safety, and mechanism of subcutaneous immunotherapy (SCIT). MethodsThe efficacy, safety, and serum immunological changes of 3 modes of subcutaneous immunotherapy were compared. Peripheral blood mononuclear cells (PBMC) transcriptome changes were obtained on the Illumina sequencing platforms. We confirmed differentially expressed genes (DEGs) by quantitative real-time polymerase chain reaction (PCR). The DEGs were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks. The correlation between the common DEGs and clinical indicators was analyzed by Origin 2022. ResultsThe 3 SCITs were all effective after 1 year. The Combined Symptom and Medication Score (CSMS) and Visual Analog Score (VAS) in rush immunotherapy (RIT) are lowest after 24 and 48 weeks of treatment among the 3 groups. After treatment, the levels of sIgE, sIgE/tIgE, Th2 cytokines, Th17 cytokines, and percentage of peripheral eosinophils (EOS%) decreased significantly (P＜0.05), while the levels of Th1 type cytokines did not change significantly. Transcriptome analysis identified 24, 24, and 91 DEGs at W3 and 42, 52, 175 DEGs at W7 in conventional immunotherapy (CIT), cluster immunotherapy (CLIT), and RIT groups, respectively. The pathways and functions involved in SCIT include secretion of Th1/2 cytokines, immune cell differentiation. Unlike CIT and CLIT, DEGs are also involved in T cell tolerance induction, T cell anergy, and lymphocyte anergy in RIT. CXCR1, CXCR2, and IER3 had a specific effect on reflecting the improvement of symptoms in allergic rhinitis patients with SCIT. ConclusionThe clinical efficacy of RIT appeared earlier than CIT and CLIT. Clinicians can use the highly conserved gene expression profile to evaluate responses to immunotherapy.

A comparison of cluster versus standard subcutaneous multi-allergen immunotherapy systemic reaction risk

Cluster schedules for subcutaneous allergen immunotherapy require significantly fewer injections, but there have been conflicting reports regarding the risk of systemic reaction. We aim to compare the incidence of systemic reactions during the build-up stages of multi-allergen standard versus cluster immunotherapy.

Role of premedication to prevent reactions in cluster immunotherapy

Role of premedication to prevent reactions in cluster immunotherapy

Observational Study on The Efficacy and Effects in The Quality of Life of Cluster Immunotherapy Schedule in Patients with Asthma Sensitized to House Dust Mites

Background: The conventional schedule administration of subcutaneous allergen immunotherapy (SCIT) for Acaroid®, requires eight weeks to get the maintenance dose. To reduce the duration of the build-up phase, the cluster schedules have been introduced. The objective was to analyze the one-year efficacy of Acaroid® in a cluster schedule, as well as the effect on the patient’s quality of life. Methods: A real-world observational study was designed, with one-year follow-up. Patients 5-65 years-old with allergic bronchial asthma, sensitized to house dust mites and treated with Acaroid®, in cluster schedule 2/2/2 were included. The main efficacy endpoint was the Asthma Control Test (ACT) score at month 12 compared to baseline. The patient’s quality of life was measured with the Asthma Quality of Life Questionnaire (AQLQ) and ESPRINT-15 questionnaire. Results: A total of 81 patients, 55.6% female, were included with a mean age of 29.7 years old. The ACT score from baseline-12 months significantly improved (p=0.003) 1.4 points (95%CI 0.4-2.4). The proportion of patients with a good asthma control increased significantly from baseline-6-12 months (p&lt;0.05). AQLQ (p=0.014) and ESPRINT-15 quality of life domains significantly improved at 12 months. Conclusions: The cluster schedule 2/2/2 of SCIT with Acaroid® was effective and allowed shortening the build-up phase to three weeks, instead of the conventional schedule of eight weeks. This resulted in the benefit of the patient in terms of comfort and could reduce the costs related to SCIT administration while maintaining patient efficacy and safety of the conventional schedules.

Risk of anaphylaxis in cluster vs standard subcutaneous multiallergen immunotherapy

BackgroundCluster schedules for subcutaneous allergen immunotherapy (AIT) require significantly fewer injections, but there have been conflicting reports regarding the risk of systemic reactions (SR). ObjectiveTo compare the incidence of SRs during the build-up stages of multiallergen standard vs cluster immunotherapy. MethodsData on SRs were collected prospectively from 91 urban adult patients who underwent either standard or cluster AIT at the Johns Hopkins Allergy and Asthma Center from 2014 to 2022. The SRs were recorded during the build-up phase and compared for both protocols using Pearson's χ2, Fisher exact test, and multivariate logistic regression models. ResultsOverall, SR rates were 21% for patients in the standard schedule and 37% for patients in the cluster immunotherapy schedule, which was not statistically different (P = .08). However, the SR rate for each injection was 0.69% per injection in the standard protocol and 2.29% per injection in the cluster schedule (incident rate ratio = 3.3). All SRs (100%) in both groups occurred in the second half of the build-up phase. Multivariate regression revealed that the target prescription protein nitrogen units and the number of allergens in the treatment vial did not influence SR rates (odds ratio = 1.00 and 1.06, respectively). ConclusionThe overall incidence of SR was not statistically different for cluster and standard AIT protocols. However, because cluster patients received approximately half the number of injections, the risk for SR per individual injection is more than 3-fold higher than that of standard immunotherapy.

Accelerated/rush allergen immunotherapy.

Accelerated allergy shot schedules for inhalant and venom allergens provide individuals with allergy symptom relief but in a shorter time frame than conventional therapy. Accelerated immunotherapy (IT) protocols allow patients to reach therapeutic doses in a shorter time frame while improving adherence and reducing direct costs (e.g., fewer office visits and medications) and indirect costs (e.g., less travel time, missed work or school). Rush IT and cluster IT are believed to work through mechanisms similar to conventional subcutaneous IT (SCIT). The risk for severe systemic reactions during accelerated IT is low when appropriately administered; however, life-threatening and fatal reactions do occur. To reduce the incidence of systemic allergic reactions during cluster and rush IT protocols, premedication is recommended. It is important to exclude individuals at high risk such as those with poorly controlled asthma or those who are on β-blockers to mitigate the risk for developing systemic allergic reactions. However, accelerated SCIT regimens offer increased convenience, faster improvement in allergy symptoms, and the potential to reduce health-care costs while providing equivalent safety outcomes compared with conventional IT protocols.

Real-life safety study of an accelerated cluster immunotherapy with a house dust mite native extract in patients with allergic rhinitis or rhinoconjunctivitis

Real-life safety study of an accelerated cluster immunotherapy with a house dust mite native extract in patients with allergic rhinitis or rhinoconjunctivitis

Observational study on the tolerability of cluster immunotherapy schedules in patients sensitized to house dust mites

Observational study on the tolerability of cluster immunotherapy schedules in patients sensitized to house dust mites

Early Efficacy Analysis of Cluster and Conventional Immunotherapy in Patients With Allergic Rhinitis.

Specific immunotherapy is an important immune-modifying treatment for patients with allergic rhinitis (AR). We compared the early efficacy and safety of cluster and conventional immunotherapies for patients with AR. One hundred forty-nine patients with persistent AR were enrolled in a randomized and open-label trial and were divided into the following 4 groups: 60 children treated conventionally, 33 children treated using the cluster schedule, 23 adults treated conventionally, and 33 adults treated using the cluster schedule. Patients in the cluster groups reached the maintenance dose within 6 weeks, while those receiving conventional therapy reached the maintenance dose within 14 weeks. Symptom scores and skin prick test scores (SPTs) were used to evaluate clinical efficacy and adverse reactions. After buildup phase of treatment, symptom scores, and SPTs were significantly lower than those prior to treatment in each group (P < .05). No significant differences were found in the efficacy of nasal symptoms scores among four groups (P > .05).However, the efficacy of SPTs using conventional schedule was higher than cluster schedule in children groups (group A and B, 57.7 vs 30.2%, P = .001). Besides, the efficacy of SPTs in adults was higher than children when using the cluster treatment (group D and B, 53.0 vs 30.2%, P = .008). No severe adverse reaction occurred. Conventional and cluster immunotherapy schedules have similar efficacies, which do not vary with age; both schedules are safe and reliable. Also, SPT facilitate evaluation of clinical efficacy.

Accelerated Immunotherapy: Why Are We Going So Slow?

Accelerated schedules for administering subcutaneous aeroallergen immunotherapy have the potential to provide convenience, reduce the cost, and improve compliance over conventional (weekly) schedules. In this review, we describe studies of cluster and rush immunotherapy (RIT), the risk of systemic allergic reactions (SARs) for various schedules, and methods to reduce that risk. Cluster schedules are associated with a slightly increased risk of a SAR that can be reduced by taking an H1 antihistamine on the day of injections. The risk of a SAR can also be reduced with depo extracts, fewer injections per cluster, and administration of fewer than 3 clusters per week. RIT is associated with a 27 to 38% risk of a SAR that can be reduced with administration of corticosteroids, an H1 and H2 antihistamine and possibly a leukotriene blocker for 3 days prior to the procedure and by stopping at a lower dose. Reactions tend to occur 1–2 h after the last injection on the day of RIT, and there is an increased risk of a reaction if subsequent weekly doses are missed. Accelerated immunotherapy schedules can offer benefits over weekly schedules; however, the increased risk of a SAR needs to be considered when deciding to recommend such a schedule.

Successful completion of an imported fire ant cluster immunotherapy protocol

Since their introduction into Mobile, Alabama, in the 1920s, imported fire ants (IFAs) have slowly spread across the Southern United States.1,2 The leading cause of hypersensitivity in IFA endemic areas among all Hymenoptera, these venomous ants can cause clinical reactions, ranging from localized sterile pustules to systemic IgE-mediated reactions, including death.3,4 Immunotherapy with IFA whole body extract (WBE) is an effective and safe treatment for IFA hypersensitivity.5–8 Both conventional and rush immunotherapy schedules have been previously reported for IFA hypersensitivity, but there are no reports of an IFA cluster schedule.

A significant decrease in the gene expression of interleukin-17 following the administration of synbiotic in patients with allergic rhinitis who underwent immunotherapy: A placebo-controlled clinical trial.

Background:Allergic Rhinitis (AR) is the most common allergic disease worldwide. The present study, evaluated effects of synbiotic on gene expression of interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-17 (IL-17), transforming growth factor beta (TGF-β), and forkhead box P3 (FoxP3) in AR patients who received concomitant immunotherapy in a placebo-controlled clinical trial.Materials and Methods:Twenty AR patients were randomized in synbiotic and placebo groups and received cluster immunotherapy for 2 months. RNA was extracted from peripheral PBMCs, then the cDNA synthesized. Subsequently, SYBR Green real-time Reverse transcription polymerase chain reaction technique was employed for studying the expression of mentioned genes. In addition, SNOT-22 and mini-Rhinoconjunctivitis Quality of Life Questionnaire questionnaires were completed by patients. Data were analyzed before and also 2 and 6 months after intervention.Results:Clinical symptoms and quality of life were improved with immunotherapy, but there was no significant difference between the placebo and synbiotic groups. Gene expression of IFN-γ, TGF-β, and FoxP3 was increased whereas the gene expression of IL-4 and IL-10 decreased, but not significant. Interestingly, the gene expression of IL-17 in the synbiotic group was significantly decreased versus placebo after 2 months (P = 0.001) and also at the end of intervention (P = 0.0001) comparing with the time zero.Conclusion:Significant reduction in the IL-17 gene expression following administration of synbiotic versus placebo shows the importance of synbiotic in control of the immunopathogenesis of AR. Further studies with more samples are recommended. In addition, evaluating the effects of synbiotic in patients who do not undergo immunotherapy is suggested to get a better conclusion.

P040 Low vitamin D and skin prick size are associated with anaphylaxis in accelerated immunotherapy

Rush and cluster immunotherapy require careful patient selection. This study examines the association of vitamin D level and skin prick wheal size with the incidence and severity of in-office anaphylaxis in a group of patients undergoing accelerated immunotherapy at a private allergy clinic.

Comparative analysis of cluster versus conventional immunotherapy in patients with allergic rhinitis.

The present study aimed to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized extract administered in conventional and cluster immunotherapy regiments for patients with persistent allergic rhinitis. A total of 60 patients with moderate to severe allergic rhinitis caused by dust mites were treated for 1 year with either conventional immunotherapy (n=30) or cluster immunotherapy (n=30). Nasal conjunctival symptoms and signs were assessed to evaluate the clinical efficacy of the two regimens, and the incidence of local and systemic adverse reactions were also evaluated. The findings demonstrated that the cluster regimen reduced the duration between the initial and maintenance dose by >60%, and resulted in a significant improvement, as compared with the conventional regimen, after 6 weeks of observation (P<0.05). However, the incidence of local and systemic adverse reactions in the cluster regimen during the dose accumulation phase and the dose maintenance phase was not significantly different, as compared with the conventional immunotherapy regimen. These results suggest that cluster immunotherapy is efficacious and safe to treat patients who are clinically sensitive to dust mites.

The study of a possible correlation between serum levels of interleukin 17 and clinical severity in patients with allergic rhinitis.

Introduction:Allergic rhinitis (AR) is one of the most common allergic diseases, which affects ∼20% of the world's population. T-helper (Th) type 2 cells produce interleukin (IL) 4 and IL-13, and mediate allergic responses, and these cytokines have been extensively studied as key players in the atopic airway diseases. However, the involvement of Th17 cells and IL-17 in AR has not been clearly examined.Aim:To reevaluate AR clinical severity with serum IL-17, whether IL-17 affects the disease alone or in contribution with the atopic predisposition.Patients and Methods:During an 18-month period, 39 individuals were divided into three groups: A, (13 control), B (13 with mild-to-moderate AR), and C (13 with severe AR). Both group B and group C patients (26) were subjected to clinical examination and allergy skin testing, and to measurement of both total serum immunoglobulin E (IgE) and IL-17 levels. Eleven patients with AR then were exposed to 6 months of cluster immunotherapy, whereas the rest of the patients were not exposed.Results:Revealed a significant elevation of serum IL-17 levels with an associated increase in serum IgE in the patients with AR compared with controls and revealed that the serum levels of both total serum IgE and IL-17 decreased significantly after cluster immunotherapy.Conclusion:These preliminary results added new data about the use of injective immunotherapy as well as reported on the use of sublingual immunotherapy.

O051 Correlation between anaphylaxis and vitamin D deficiency in patients undergoing accelerated immunotherapy

There has been epidemiological and clinical data showing the association of vitamin D deficiency (VDD) with anaphylaxis. The purpose of this study is to assess the impact of vitamin D levels on severity of anaphylaxis in patients undergoing rush and/or cluster (RC) immunotherapy.

Immunologic alterations and efficacy of subcutaneous immunotherapy with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients

BackgroundThere is a continuing debate about whether monoallergen subcutaneous immunotherapy (SCIT) is able to modulate immune and clinical responses toward main causal allergen in polysensitized patients. ObjectiveTo investigate short-term immunologic changes and clinical effectiveness of SCIT with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients who have rhinitis with or without asthma. MethodsNineteen monosensitized and 24 polysensitized patients participated in this prospective, self-placebo-controlled, interventional study. Cluster immunotherapy with D pteronyssinus was administered after 2 months of placebo in both groups. Immunologic parameters, including CD203c expression on basophils after allergen stimulation, total IgE, specific IgE, and specific IgG4, were evaluated at baseline, after placebo, and after immunotherapy. Clinical effectiveness was assessed using monthly symptom-medication scores, visual analog scale, quality-of-life questionnaire, and nasal allergen provocation test. ResultsAt baseline, polysensitized patients had higher CD203c expression on basophils than monosensitized patients (P = .007). Activated basophils expressing CD203c, total IgE, and specific IgG4 were significantly increased after immunotherapy compared with baseline and placebo in the polysensitized group (P < .025). After immunotherapy, specific IgE and D pteronyssinus–induced CD203c expression were significantly higher in polysensitized than monosensitized patients (P < .05). The total symptom scores and the Mini Rhinoconjunctivitis Quality of Life Questionnaire scores in polysensitized patients and the visual analog scale scores in both groups were lower after immunotherapy compared with baseline and placebo (P < .025). Titrated nasal allergen provocation test with D pteronyssinus increased after immunotherapy in the monosensitized group (P < .05). ConclusionThis study indicates that monosensitized and polysensitized patients have distinct humoral response and basophil behavior to SCIT. However, a single-allergen immunotherapy corresponding to the most clinically troublesome allergy in polysensitized patients can lead to early clinical efficacy comparable to that seen in monosensitized patients. Trial Registrationclinicaltrials.gov Identifier: NCT01795846.

The Safety of Cluster Immunotherapy Compared to Conventional Immunotherapy

There is a lack of information regarding the safety profile of accelerated protocols for subcutaneous allergen immunotherapy (SCIT), such as cluster immunotherapy. We conducted a prospective safety study of allergic patients who chose to receive multi-aeroallergen immunotherapy by either cluster or conventional build-up schedules at the Johns Hopkins Asthma and Allergy Center. Cluster patients were scheduled to receive a series of 15 injections over the course of five weekly visits. Conventional immunotherapy patients received 26 weekly injections. Inclusion criteria were the same for both groups and allergen target dosing was identical. Cluster patients required antihistamine pretreatment 30 minutes prior to each visit. We examined the rates of local (LR) and systemic reactions (SR). Eight of 13 patients completed the planned cluster immunotherapy schedule, while four achieved maintenance dosing upon converting to conventional SCIT. Sixteen patients completed conventional immunotherapy. One patient stopped immunotherapy altogether. Five patients experienced systemic reactions in the cluster group (38%), three of which required the administration of epinephrine. Two patients experienced systemic reactions during conventional immunotherapy (12.5%), one of which required epinephrine. Five systemic reactions occurred from 1:1 dilutions, while two occurred from 1:10 dilutions. All systemic reactions were grade I or II except one grade III reaction in the conventional immunotherapy group. All systemic reactions occurred within 60 minutes of an injection. A cluster protocol can be used to deliver multi-allergen immunotherapy. The reactions observed in the cluster group will be compared to patients who receive conventional immunotherapy build-up over a two-year period.