Allergen Immunotherapy Research Articles

Application of Innovative Digital Medical Technologies of Bioquantum Medicine and Therapy in Elimination of Allergy Symptoms

In recent years, there has been an increasing integration of alternative medical technologies, particularly those involving digital medical technologies based on quantum and bioquantum medicine, frequency and wave therapy, and bioquantum therapy, for treating COVID-19, post-COVID, and long-COVID conditions as outlined in ICD-11. This study aimed to experimentally evaluate the latest digital medical technologies, specifically focusing on bioquantum therapy, for allergy treatment. A comprehensive review of existing literature on the application of bioquantum medicine in allergy therapy was conducted. The findings confirm that bioquantum therapy is an effective treatment option for mild to moderate allergies, significantly enhancing symptoms and overall quality of life. BICOM devices are recommended for managing mild to moderate allergies and associated complications. Furthermore, the study highlights that BICOM therapy is not only effective but also safe, with no serious adverse effects observed throughout the year-long study period. Given these promising results, it is recommended that healthcare professionals pursue specialized training, including master classes and continuous professional development in bioquantum medicine and therapy. Obtaining the necessary licenses and permits to work with BICOM devices is essential for ensuring the safe and effective application of this innovative treatment method. As the field continues to evolve, staying updated on the latest advancements in bioquantum medicine will be crucial for medical practitioners.

Pollen effects in a changing climate: Ragweed pollen exposure and sleepiness in immunotherapy patients of a Southeastern Michigan allergy clinic.

Allergic rhino-conjunctivitis (AR) is a globally relevant health disorder characterized by sneezing, rhinorrhea and sleep disturbance. Ragweed (Ambrosia artemisiifolia) is a plant common to North America and an important allergen. Coarse methods of measuring airborne pollen counts are used to predict seasonal allergy symptoms. This research used a longitudinal study design with a novel, model-based raster of predicted pollen counts to test associations with self-reported symptoms of AR collected from patients receiving immunotherapy for pollen allergies at an allergy clinic. Researchers visited a clinic six times over three weeks. Immunotherapy patients were asked to fill out a brief intake survey on allergic and symptomatic profiles, daytime sleepiness, housing quality, and demographics. Participants responded to a daily, emailed survey on sleepiness and asthma symptoms for 21 days. Using the date and location of responses, ragweed pollen counts were extracted from a prognostic, model based raster (25km pixels). Lag associations of pollen counts with sleepiness were tested using a logistic regression model , adjusted for housing and demographic characteristics, in a distributed lag non-linear model (DLNM) framework. 49 people participated in the study. 26 (52%) were female. The mean age was 37.9 years. Asthma/allergy symptoms were not associated with ragweed pollen but sleepiness was highest two days after exposure (Estimate: 0.33 [0.04,0.62]). Subjects traveled widely during the study period. Intense exposures to ragweed pollen may be associated with daytime sleepiness within small exposure windows. Model-based predicted pollen counts could be used to study health impacts of pollen in people with disease severe enough to receive immunotherapy. Daytime sleepiness can affect productivity and injury risk, and pollen season length and allergenicity may be increasing with climate change. Thus our results may have important implications for population health.

Analysis of the immunomodulatory properties of mycobacterium cell wall fraction on the cytokine production of peripheral blood mononuclear cells of healthy dogs.

Mycobacterium cell wall fraction (MCWF) is derived from nonpathogenic Mycobacterium phlei and is used as an immunomodulatory compound in clinical practice, yet its mode-of-action requires further research. To evaluate the host response to MCWF in canine peripheral blood mononuclear cells (PBMCs) by using enzyme-linked immunosorbent assays (ELISA) and quantitative reverse transcription (qRT)-PCR for assessment of cytokines. Eight healthy Labrador retrievers. PBMCs were isolated from whole blood using density centrifugation. The cells were cultured with different concentrations of MCWF or a potent stimulator of cytokine production, phorbol 12-myristate 13-acetate/ionomycin, or left in cell culture medium for 24, 48 and 72 h. Cytokines were measured by ELISA for interleukin (IL)-4, IL-10 and interferon-gamma (IFN-γ), and by qRT-PCR for IL-4, IL-10, IL-13, IFN-γ, tumour necrosis factor alpha (TNF-α) and transforming growth factor-beta. A significant increase of IL-10 messenger ribonucleic acid (mRNA) was detected at all time points for all concentrations of MCWF (p < 0.05). Protein analysis reflected this finding, with a maximum IL-10 concentration of 300.6 ± 38.3 μg/mL. Compared to the negative control, post-stimulation elevation of IFN-γ mRNA was noted at 24 h with all concentrations of MCWF (p < 0.01), and TNF-α mRNA was increased for 0.5 μg/dL MCWF only at 72 h (p < 0.05). MCWF stimulation of PBMCs results in the elevation of both proinflammatory and regulatory cytokine mRNA. Further research into the role of MCWF as a systemically administered regulatory immunomodulator or adjuvant to allergen-specific immunotherapy should be considered.

The impact of adverse reactions on adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy in Japan

Background Allergen immunotherapy is the only treatment that can achieve remission for allergic diseases. Aims/Objectives To investigate the three-year adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy at a clinic in Japan and identify factors that influence adherence and severe adverse reactions. Material and Methods In total, 174 patients aged 12 years or older who started sublingual immunotherapy for Japanese cedar pollinosis (n = 72), house dust mite allergy (n = 55), or both (n = 47) between May 2017 and June 2018. Patient age, sex, type of pharmacotherapy used, adverse reactions, blood test results, and duration of continuous treatment were investigated. Results The three-year treatment continuation rate was 40.8%. Adverse reaction rates were 12.6% for cedar pollinosis and 40.2% for house dust mite allergy. Patients with dose reductions due to severe reactions had lower first-year continuation rates. In the MITICURE® group, patients with severe reactions had significantly higher serum total IgE levels. Severe reactions were more common in MITICURE® patients with seven or more positive antigen types. Conclusions and Significance Severe adverse reactions reduced early adherence.

Efficacy and safety of subcutaneous and sublingual allergen immunotherapy in the treatment of asthma in children: a systematic review and meta-analysis.

Asthma is a common chronic condition in children globally. Allergen-specific immunotherapy, such as subcutaneous (SCIT) and sublingual (SLIT) therapies, are promising by increasing allergen tolerance. This meta-analysis compares the efficacy and safety of SLIT and SCIT in pediatric asthma. We searched PubMed, Cochrane Library, and Embase for randomized controlled trials and case-control studies comparing SLIT and SCIT in asthmatic children. Meta-analysis was conducted using random-effects models with calculations via R software version 4.3.2 and RevMan version 5.4. Study quality and bias risk were assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool. The literature search yielded a total of 1787 records, with 7 studies meeting the inclusion criteria after screening and assessments. There was no significant difference in the Total Asthma Symptoms Score between SLIT and SCIT (mean difference -0.05 [95% CI: -0.21; 0.10]). However, asthma improvement rates were higher in the SLIT group (risk ratio 0.77 [95% CI: 0.64; 0.93]). FEV1 improvement showed no significant difference (mean difference -1.60 [95% CI: -6.27; 3.08]). Adverse events were similar between the treatments (risk ratio 0.56 [95% CI: 0.11; 2.82]). SLIT and SCIT were generally similarly effective and safe for treating pediatric asthma. SLIT may be preferred due to its noninvasive administration. More research is needed on long-term effects and tailored treatment approaches.

RIAIT (Italian Registry of Allergen Immunotherapy): Protocol for a New Tool in a New Vision of Disease-Modifying Therapy for Allergists.

Randomized controlled trials have demonstrated responses to clinical parameters, but a significant proportion of allergy patients in real-life settings would have been excluded from such studies. Therefore, real-world research is needed, and there is a growing body of information on allergen immunotherapy's long-term effectiveness and safety. Real-world evidence can be a valuable instrument to better understand the patient's journey and the effectiveness and safety of therapies. For this purpose, a registry will be used for the first time in Italy to evaluate the impact of allergen immunotherapy on several outcomes, including quality of life and disease-related effects in the pediatric and adult allergic population with a socio-economic assessment and respect to real-world health.

Evaluation of Scoring Atopic Dermatitis (SCORAD) and scratching behavior in BALB/c mice treated with house dust mite immunotherapy

Allergen specific immunotherapy controls the reaction and builds immunological tolerance by giving an allergen in escalating doses. Research on immunotherapy in atopic dermatitis (AD) mouse model offers a new perspective on the approach of treatment in AD. This was an experimental study of 33 male BALB/c mice, 6-8 weeks old, divided into 3 groups (control, AD model, and house dust mite/HDM immunotherapy). The mice received spray and patch containing allergen extract of Dermatophagoides pteronyssinus. Immunotherapy was injected subcutaneously in increasing doses. The evaluation of SCORAD and scratching behavior were observed at the end of the treatment on day 93. The SCORAD of the model group that received HDM allergen had a mean of 1.27 ± 0.467 and the immunotherapy group had a mean of 0.36 ± 0.505. There were significant differences between the groups. The model group had a mean of 5.18 ± 4.119 and the immunotherapy group had mean of 1.55 ± 1.293. The statistical analysis showed that there were significant differences between control group and model group, as well as model group and immunotherapy group. Interobserver agreement was assessed and showed substantial agreement for SCORAD (ĸ = 0.613 and p &lt; 0.001) and scratching evaluation (ĸ = 0.714 and p &lt; 0.001). House dust mite immunotherapy significantly reduced SCORAD and scratching behavior in BALB/c mice compared to placebo groups.

Impact of COVID-19 on adverse reactions to subcutaneous specific immunotherapy in children:a retrospective cohort study

BackgroundCOVID-19 is a new infectious disease. To investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the adverse reactions of subcutaneous specific immunotherapy (SCIT) in children.MethodsThis study was conducted by collecting relevant data from children who underwent house dust mite SCIT from April 3, 2021, to March 18, 2023, including information on the time of COVID-19 infection, symptoms, and adverse reactions after each allergen injection. A mixed effects model was used to analyze the changes in adverse reactions before and after the COVID-19 infection.ResultsAmong the records of adverse reactions from 2658 injections in 123 children who underwent SCIT, the overall adverse reaction rate before COVID-19 infection was 39.8% and 30.0% after COVID-19 infection. Compared with pre-infection with COVID-19, the risks of overall adverse reactions, local adverse reactions, and systemic adverse reactions of immunotherapy after COVID-19 infection were reduced (odds ratio [OR] = 0.24, 0.31, and 0.28, all P < 0.05). Among the local adverse reactions, the incidence of the unvaccinated group was the highest (15.3% vs. 7.1%). The incidence of overall and local adverse reactions to SCIT decreased in 2-vaccinated COVID-19 recipients (OR = 0.29–0.31, P < 0.05).ConclusionsIn children, SARS-CoV-2 infection does not increase the incidence of adverse reactions to SCIT. This finding can provide a basis for the implementation of allergen-specific immunotherapy (AIT) during the COVID-19 pandemic.

Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells

Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B cells (Bmem) are phenotypically altered after 4 months of sublingual AIT for ryegrass pollen allergy. Whether these effects are shared with subcutaneous allergen immunotherapy (SCIT) and affect the epitope specificity of Bmem remain unknown. The study aimed to evaluate the phenotype and antigen receptor sequences of Bmem specific to the major bee venom (BV) allergen Api m 1 before and after ultra-rush SCIT for BV allergy. Recombinant Api m 1 protein tetramers were generated to evaluate basophil activation in a cohort of individuals with BV allergy before and after BV SCIT. Comprehensive flow cytometry was performed to evaluate and purify Api m 1-specific Bmem. Immunoglobulin genes from single Api m 1-specific Bmem were sequenced and structurally modeled onto Api m 1. SCIT promoted class switching of Api m 1-specific Bmem to IgG2 and IgG4 with increased expression of CD23 and CD29. Furthermore, modeling of Api m 1-specific immunoglobulin from Bmem identified a suite of possible new and diverse allergen epitopes on Api m 1 and highlighted epitopes that may preferentially be bound by immunoglobulin after SCIT. AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.

Retrospective, Real Life Study on the Effectiveness and Safety of a Depigmented-Polymerized Subcutaneous Vaccine Containing a Mixture of Grasses and Olea europaea

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions. Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients’ symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed. Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment. Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments.

Alterations in immunized antigens of Anisakis pegreffii by ampicillin-induced gut microbiome changes in mice.

The gut microbiome plays an essential role in host immune responses, including allergic reactions. However, commensal gut microbiota is extremely sensitive to antibiotics and excessive usage can cause microbial dysbiosis. Herein, we investigated how changes in the gut microbiome induced by ampicillin affected the production of IgG1 and IgG2a antibodies in mice subsequently exposed to Anisakis pegreffii antigens. Ampicillin treatment caused a notable change in the gut microbiome as shown by changes in both alpha and beta diversity indexes. In a 1-dimensional immunoblot using Anisakis-specific anti-mouse IgG1, a 56-kDa band corresponding to an unnamed Anisakis protein was detected using mass spectrometry analysis only in ampicillin-treated mice. In the Anisakis-specific anti-mouse IgG2a-probed immunoblot, a 70-kDa band corresponding to heat shock protein 70 (HSP70) was only detected in ampicillin-treated and Anisakis-immunized mice. A 2-dimensional immunoblot against Anisakis extract with immunized mouse sera demonstrated altered spot patterns in both groups. Our results showed that ampicillin treatment altered the gut microbiome composition in mice, changing the immunization response to antigens from A. pegreffii. This research could serve as a basis for developing vaccines or allergy immunotherapies against parasitic infections.

Local Allergic Rhinitis-A Challenge for Allergology and Otorhinolaryngology Cooperation (Scoping Review).

Local allergic rhinitis (LAR) represents a medical provocation for allergists and otorhinolaryngologists. LAR is considered to be a subtype of allergic rhinitis (AR) that affects a great percentage of patients who were, for decades, diagnosed as having chronic non-allergic rhinitis. The clinical picture is represented by rhinorrhea, sneezing, and nasal itching correlated with specific pollen season or dust, mold, or pet interior exposure. Usual assessment of AR (skin prick testing and serum IgE assessment) produces negative results. Specialized centers in allergology and ENT around the globe use a nasal allergen challenge, assessment of local IgE, basophil activation test (BAT), and nasal cytology in the diagnostic approach to the disease, taking into account their current limitations. The impact of LAR on quality-of-life indicators is the same as in AR. Treatment for LAR is similar to that for AR and is the same as for AR: allergen exposure avoidance, drug therapy, and allergen immunotherapy. This scoping review gathers the current up-to-date open access evidence available on PubMed on the subject of LAR.

Advancements in food allergen immunotherapy: improving quality of life and reducing risks.

Advancements in food allergen immunotherapy: improving quality of life and reducing risks.

DNA Meets Protein─Development, Characterization, and Application of Aptamers against Peanut Allergen.

Allergen detection methods support food labeling and quality assessment at the allergen component level of allergen preparations used for allergy diagnosis and immunotherapy (AIT). Commonly applied enzyme-linked immunosorbent assay (ELISA) requires animal antibodies but potentially shows batch variations. We developed synthetic aptamers as alternative binders in allergen detection to meet the replacement, reduction, and refinement (3R) principle on animal protection in science. ssDNA aptamers were specifically selected against the major peanut allergen Ara h 1 and identified by next-generation sequencing. Application in various detection systems (ELISA-like assays, western blot, and surface plasmon resonance) was demonstrated. The ELISA-like assay comprised a sensitivity of 10 ng/mL Ara h 1, comparable to published antibody-based ELISA, and allowed Ara h 1 detection in various peanut flours, similar to those used in peanut AIT as well as in processed food. This ELISA-like aptamer-based assay proofs antibody-free allergen detection for food labeling or quality assessment of diagnostic and therapeutic allergen products.

Forecast models for start and peak dates of Poaceae pollen season in Tétouan (NW Morocco) using multiple regression analysis.

Poaceae pollen is one of the most widespread sources of aeroallergens in the world. The aim of this study is to build predictive models for the pollen season start day (PSsd) and peak dates of the Poaceae pollen season and thus give an overview of the climatic parameters that have the greatest influence. In Tétouan, sampling was carried out using a volumetric spore trap of the Burkard Hirst type. The relationships between the PSsd, peak dates and meteorological parameters were determined using correlation analysis. The models were constructed using multiple regression analysis with data from 2008 to 2019 and tested on data from 2022. The PSsd was especially significantly influenced by minimum temperature during winter and precipitation in the autumn of the previous year. The peak dates were significantly correlated with precipitation in January, March and April, but not with temperature. Three models were obtained for each of the season's parameters; the most accurate model for the PSsd explained a variability of 61% and includes as main predictors rainfall from the autumn of the previous year and the mean daily average temperature from 23 February to 8 March. The two most efficient peak dates models included precipitation in January and April as the main predictor variables, and explained greater variability (87 and 88%). Precipitation in autumn and the mean daily and the sum of minimum temperature in winter, showed significant decreasing tendencies. However, the PSsd trend delay was not statistically significant. This study draws the importance of the weather during preseason for grass pollen production and emphasises the usefulness of the models for allergic patients to take preventive measures and for healthcare professionals in allergy therapy.

Management of Allergic Rhinitis in the United Arab Emirates: Expert Consensus Recommendations on Allergen Immunotherapy.

Allergic rhinitis (AR) is a chronic inflammatory condition of the upper airways caused by a type I hypersensitivity reaction triggered by environmental allergens. AR is associated with significant morbidity and affects patients' quality of life, emotional well-being, productivity, and cognitive functioning. As AR prevalence and morbidity have increased significantly worldwide, similar observations have been noted in the United Arab Emirates (UAE) with AR becoming a potential public health issue. Management of AR in the UAE is mainly provided by non-allergy specialists relying on first-line treatments such as intranasal steroids and antihistamines, with often suboptimal and short-term efficacy. Allergen Immunotherapy (AIT) is the only currently available disease-modifying treatment option in the form of either subcutaneous or sublingual allergen immunotherapy that has been proven to have long-term benefits. This article aims to provide recommendations regarding the use of AIT for managing AR in the UAE, considering both the current landscape in the Emirati healthcare system and local experience.

Regulation of Tert methylation alleviates food allergy via regulating the Tert-IL10 signal pathway.

The cause of food allergy (FA) is still a mystery. Telomerases are involved in the regulation of immune responses. This study aims to gain an understanding of the contribution of telomerase reverse transcriptase (TERT) to the pathogenesis of FA. A murine FA model was established with ovalbumin as the specific antigen. The role of TERT in regulating dendritic cell (DC) immune tolerogenic functions was evaluated in this murine model. We observed that the Tert promoter was at demethylation status and the Tert expression was elevated in DCs of FA mice. The Tert expression in DCs had a positive correlation with the FA response. TERT prevented the induction of Il10 expression in DCs. The immune tolerogenic functions of DCs were diminished by TERT. The immune tolerogenic functions of DC were restored by CpG by boosting the Tert promoter methylation. Administration of CpG promoted the therapeutic effects of allergen specific immunotherapy in FA mice. Low levels of Il10 expression and high levels of Tert expression were observed in intestinal DCs of FA mice. CpG exposure restored the expression of Il10 and increased the therapeutic benefits of allergen-specific immunotherapy.

Macropinocytosis Is the Principal Uptake Mechanism of Antigen-Presenting Cells for Allergen-Specific Virus-like Nanoparticles.

Virus-like nanoparticles (VNP) are regarded as efficient vaccination platforms and have proven to be useful for the non-anaphylactogenic delivery of allergen-specific immunotherapy in preclinical models previously. Herein, we sought to determine the mode of VNP uptake by antigen presenting cells (APC). Accordingly, we screened a collection of substances known to inhibit different uptake pathways by APC. The human leukemia monocytic cell line THP-1 and the murine dendritic cell line DC 2.4 were examined for the uptake of fluorescently labelled VNP in the presence or absence of inhibitors. The inhibitory effect of candidate substances that blocked VNP uptake in APC lines was subsequently evaluated in studies with primary APC present in splenocyte and lung cell homogenates in vitro and upon intratracheal application of VNP in vivo. The uptake of allergen-specific VNP in vitro and in vivo was mainly observed by macrophages and CD103+ dendritic cells and was sensitive to inhibitors that block macropinocytosis, such as hyperosmolarity induced by sucrose or the polyphenol compound Rottlerin at low micromolar concentrations but not by other inhibitors. Also, T-cell proliferation induced by allergen-specific VNP was significantly reduced by both substances. In contrast, substances that stimulate macropinocytosis, such as Heparin and phorbol myristate acetate (PMA), increased VNP-uptake and may, thus, help modulate allergen-specific T-cell responses. We have identified macropinocytosis as the principal uptake mechanism of APC for allergen-specific VNP in vitro and in vivo, paving the way for further improvement of VNP-based therapies, especially those that can be used for tolerance induction in allergy, in the future.

Mannan‑, VLP-, and flagellin-based adjuvants for allergen-specific immunotherapy: a review of the current literature

Mannan‑, VLP-, and flagellin-based adjuvants for allergen-specific immunotherapy: a review of the current literature

Enhanced Gut Microbiome Capacity for Amino Acid Metabolism is associated with Peanut Oral Immunotherapy Failure.

Peanut Oral Immunotherapy (POIT) holds promise for remission of peanut allergy, though treatment is protracted and successful in only a subset of patients. Because the gut microbiome is linked to food allergy, we sought to identify fecal microbial predictors of POIT efficacy and to develop mechanistic insights into treatment response. Longitudinal functional analysis of the fecal microbiome of children (n=79) undergoing POIT in a first double-blind, placebo-controlled clinical trial, identified five microbial-derived bile acids enriched in fecal samples prior to POIT initiation that predicted treatment efficacy (AUC 0.71). Failure to induce disease remission was associated with a distinct fecal microbiome with enhanced capacity for bile acid deconjugation, amino acid metabolism, and increased peanut peptide degradation in vitro . Thus, microbiome mechanisms of POIT failure appear to include depletion of immunomodulatory secondary bile and amino acids and the antigenic peanut peptides necessary to promote peanut allergy desensitization and remission.