Allergen Immunotherapy Research Articles

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.

Routinely Used and Emerging Diagnostic and Immunotherapeutic Approaches for Wheat Allergy.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo routinely used allergy tests such as a wheat allergen-specific skin prick test (SPT), a blood test for specific immunoglobulin E (sIgE) levels, or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its emerging diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis, and the basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability, and safety of related clinical trials will then be discussed.

Single-Domain Antibodies-Novel Tools to Study and Treat Allergies.

IgE-mediated allergies represent a major health problem in the modern world. Apart from allergen-specific immunotherapy (AIT), the only disease-modifying treatment, researchers focus on biologics that target different key molecules such as allergens, IgE, or type 2 cytokines to ameliorate allergic symptoms. Single-domain antibodies, or nanobodies, are the newcomers in biotherapeutics, and their huge potential is being investigated in various research fields since their discovery 30 years ago. While they are dominantly applied for theranostics of cancer and treatment of infectious diseases, nanobodies have become increasingly substantial in allergology over the last decade. In this review, we discuss the prerequisites that we consider to be important for generating useful nanobody-based drug candidates for treating allergies. We further summarize the available research data on nanobodies used as allergen monitoring and detection probes and for therapeutic approaches. We reflect on the limitations that have to be addressed during the development process, such as in vivo half-life and immunogenicity. Finally, we speculate about novel application formats for allergy treatment that might be available in the future.

The Correlation between Oral Health and Air Pollution: A Systematic Review.

This systematic review assessed to evaluate the potential correlation between oral health and air pollution. To the best of the authors' knowledge, this is the first systematic review endeavoring to compare air pollution and oral health. A systematic search was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement and employed the PICO(S) approach (Patient or Population, Intervention, Control or Comparison, Outcome, and Study types). The search was limited to English-language articles, and publications within a 15-year timeframe were included in the electronic search. A comprehensive search was conducted across PubMed, Scopus, Embase, and Web of Science databases, spanning the years 2008 to 2023, resulting in a total of 4983 scientific articles. A final selection of 11 scientific papers was made based on their study type and the specific air pollutants examined. The selected papers analyzed various air pollutants associated with health-related diseases, including Ozone, Nitrogen Dioxide, Nitrogen Monoxide, Carbon Monoxide, sulfur dioxide, and particulate matter. Three out of eleven of the reviewed studies assert a strong correlation between air pollutants and oral diseases, specifically periodontitis. However, the exact biological mechanisms underlying this correlation do not seem to be fully understood, indicating the need for further comprehensive investigation in this regard. Dentists can contribute to the collective effort by educating their patients about the oral health implications of air pollution, thereby supporting initiatives aimed at promoting environmental and health sustainability.

Allergen-specific B cell responses in oral immunotherapy-induced desensitization, remission, and natural outgrowth in cow's milk allergy.

Antigen-specific memory B cells play a key role in the induction of desensitization and remission to food allergens in oral immunotherapy and in the development of natural tolerance (NT). Here, we characterized milk allergen Bos d 9-specific B cells in oral allergen-specific immunotherapy (OIT) and in children spontaneously outgrowing cow's milk allergy (CMA) due to NT. Samples from children with CMA who received oral OIT (before, during, and after), children who naturally outgrew CMA (NT), and healthy individuals were received from Stanford biobank. Bos d 9-specific B cells were isolated by flow cytometry and RNA-sequencing was performed. Protein profile of Bos d 9-specific B cells was analyzed by proximity extension assay. Increased frequencies of circulating milk allergen Bos d 9-specific B cells were observed after OIT and NT. Milk-desensitized subjects showed the partial acquisition of phenotypic features of remission, suggesting that desensitization is an earlier stage of remission. Within these most significantly expressed genes, IL10RA and TGFB3 were highly expressed in desensitized OIT patients. In both the remission and desensitized groups, B cell activation-, Breg cells-, BCR-signaling-, and differentiation-related genes were upregulated. In NT, pathways associated with innate immunity characteristics, development of marginal zone B cells, and a more established suppressor function of B cells prevail that may play a role in long-term tolerance. The analyses of immunoglobulin heavy chain genes in specific B cells demonstrated that IgG2 in desensitization, IgG1, IgA1, IgA2, IgG4, and IgD in remission, and IgD in NT were predominating. Secreted proteins from allergen-specific B cells revealed higher levels of regulatory cytokines, IL-10, and TGF-β after OIT and NT. Allergen-specific B cells are essential elements in regulating food allergy towards remission in OIT-received and naturally resolved individuals.

Breakthroughs in Food Allergy Therapy

Breakthroughs in Food Allergy Therapy

A recent patent in allergy & immunology: Biomarkers on allergen-specific memory B cells to predict allergen immunotherapy outcome.

A recent patent in allergy & immunology: Biomarkers on allergen-specific memory B cells to predict allergen immunotherapy outcome.

Immunomodulatory effect of PLGA-encapsulated mesenchymal stem cells-derived exosomes for the treatment of allergic rhinitis.

Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases. In order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo. The results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos. For the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment.

COVID-19 Infection in a Group of Egyptian Children with Bronchial Asthma: A Single Center Study

Abstract Background Impact of asthma on COVID-19 severity and outcome in infants is not well investigated. Therefore, we sought to assess the presentation, severity and outcome of COVID-19 infection in a group of Egyptian asthmatic children. Patients and Methods We conducted an observational follow up study on 30 asthmatic children with probable/confirmed COVID-19, aged 6-10 years, who were enrolled consecutively from the Emergency department and Isolation Ward, Children`s Hospital, Ain Shams University, Egypt. COVID-19 clinical manifestations, severity and outcome were studied. Results The median age of the children was 9 years (IQR: 6-18 years). Out of the 30 studied patients, we had 9 boys and 21 girls. COVID-19 was asymptomatic in 2/30 (6.7%), mild in 20/30 (66.7%), and severe in 8/30 (26.7%). Clinical manifestations of COVID-19 included constitutional (22,73.3%), respiratory (21, 70%), gastrointestinal (7, 23%), cardio- vascular (5, 16.7%), and dermatological (1, 3.3%) manifestations. Multisystem inflammatory syndrome (MIS-c) was diagnosed in only one patient. Chest X-ray abnormalities were found in (36.7%). The median duration of hospital stay was 10 days, Complete resolution was the final outcome of all patients. Conclusion Asthma does not represent a risk of severe COVID-19 or poor outcome and COVID-19 course, and the outcome in asthmatic children is similar to the general pediatric population. However, our study is limited by the small sample size and short duration of follow-up. Further longitudinal studies are needed to investigate the exact impact of different SARS-CoV-2 variants with respect to asthma phenotypes and asthma biological treatments and allergen immunotherapies in children.

Advancements in Food Safety: From Novel Approaches to Controversies and One Health Perspectives

This comprehensive study focus into various facets of food safety, covering controversial topics such as the bisphenol A (BPA) tolerable daily intake set by EFSA and challenges in aggregating data from food allergen immunotherapy trials. It also explores the evaluation of isomaltulose syrup as a novel food and emphasises the significance of a One Health perspective in addressing pathogenic Clostridia. Additionally, the study highlights the pivotal role of genomic resources in understanding persistence and virulence. Through a multidisciplinary lens, the study provides insights into current advancements, offering a scientific understanding of the evolving landscape of food safety.

Molecular allergen IgE tests show neosensitizaions occurring during house dust mite specific immunotherapy

Objective:Neosensitizations may be occur during the allergen specific immunotherapy（AIT） due to the differences between allergen vaccine's content and a patient's molecular sensitization profile. This study investigates whether AIT with HDM extract changes the sensitization profile, whether de novo sensitization occurs, and the clinical importance of the neosensitization. Methods:Fifty-three patients with HDM allergic rhinitis ,with/without asthma, patients were received one year HDM subcutaneous AIT . Fourteen patients were recruited as control group and received only necessary medications. Serum samples were collected at baseline, 6thmoths and 12thof AIT, respectively. Serum samples were tested specific IgE against Der p, Der p 1/2/3 and Der f, Der f 1/2/3, as well as IgG4 against Der p, Der p 1/2 and Der f, Der f 1/2. VAS were collected at the time-points as well. Results:In AIT group, Der p, Der p 1/3, and Der f 1/3 specific IgE levels were significantly higher after one-year treatment, especially for Der p 3. There were 69.2%（18/26） patients whose Der p 3 specific IgE below 0.35 kU/L at baseline but became positive（>0.35 kU/L） after treatment, that is, neosensitization occurred. All tested allergen specific IgG4 level significantly increased after one year AIT treatment and the VAS declined dramatically. However, for patients with neosensitization and without neosensitization, there were no significantly changes concerning to IgG4 level and VAS. Conclusion:Patients undergoing AIT might have a risk of neosensitization to the allergen components in the vaccines. However, the clinical importance of the neosensitization remains unclear and warrants further studies.

House dust mite immunotherapy: A real-world, prescription data-based analysis.

House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long-term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real-world evidence studies are available. We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: -34.0%, p<0.0001; oSCIT: -25.7%, p<0.0001; SLIT: -37.7%, p=0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: -45.2%, p<0.0001; oSCIT: -32.9%, p<0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p=0.0476; oSCIT OR: 0.815, p=0.0339). Real-world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR.