Allergen Immunotherapy Research Articles

Allergen immunotherapy effectiveness in specific nasal reactivity of children with local allergic rhinitis.

Background.Allergen immunotherapy (AIT) is the only disease-modifying treatment in allergy. Its efficacy has been demonstrated in the treatment of Local Allergic Rhinitis (LAR) in adults. This study intends to evaluate the effectiveness of AIT in specific nasal reactivity of paediatric patients with LAR. Methods.Patients diagnosed with LAR to Dermatophagoides pteronyssinus (Dp) were submitted to subcutaneous AIT (SCIT) (depigmented-polymerized Dp allergen extracts) for 3 years. Nasal allergen challenge (NACs) with Dp extract were performed before and 3 years after AIT. NAC response was assessed with peak nasal inspiratory flow (PNIF) and symptom score of Lebel. NACs were considered positive when there was a flow decrease of ≥ 20% in PNIF and a score of symptoms ≥ 3 points. Demographic data and NAC results were analysed. Results.We included 32 paediatric patients (mean age 9.9±3.08 years, 18 female) and 10 adult patients, (mean age 30.4±12.2 years, 7 female). The symptom score obtained at the 1st minute, 5th minute, 15th minute and 30th minute in response to NAC, were reduced after AIT. The nasal inspiratory flow decrease induced by NAC was also reduced after AIT. This reduction in nasal reactivity was observed in paediatric and in adult patients, both with statistical significance. Conclusions.AIT induced a decrease in Dp-nasal specific reactivity in children with LAR. This decline of nasal response to allergen exposure, after AIT treatment, emphasis the interest of this therapeutic approach in LAR, even in paediatric patients.

Allergic rhinitis – a review of current diagnostic and therapeutic methods

Allergic rhinitis (AR) is a common disease characterized by inflammation of the nasal mucosa caused by exposure to allergens such as pollen, house dust mites, animal dander, and molds. Symptoms include sneezing, nasal itching, watery discharge, and nasal congestion, often associated with conjunctivitis. AR can significantly reduce patients' quality of life, affecting their ability to perform daily activities and causing sleep disturbances and fatigue. Diagnosis of AR is based on a past medical history, assessment of clinical symptoms, and allergy tests, such as skin tests, and measure of specific class E (IgE) immunoglobulins in blood serum level. Treatment includes allergen avoidance, pharmacotherapy, and allergen immunotherapy. Antihistamines, intranasal glucocorticosteroids, cromones, and anti-leukotriene drugs are the basis of pharmacotherapy, helping to control symptoms and improve a patient's quality of life. Allergen immunotherapy, both subcutaneous and sublingual, is effective in modifying the course of the disease and reducing hypersensitivity to allergens. New therapeutic and diagnostic approaches, such as biomarkers and biologics, are under investigation and may offer more personalized and effective AR treatment in the future. A holistic approach to AR, including patient education and lifestyle modification, is crucial for long-term therapeutic success. The article aims to review current diagnostic and therapeutic methods used in AR.

Real-world evidence of allergen immunotherapy.

The full understanding of the long-term effectiveness and safety of allergen immunotherapy (AIT) for allergic respiratory diseases cannot be achieved through randomized controlled trials (RCTs) alone. However, real-world studies designed as registries can complement RCTs. The significance of registries is highlighted by their potential to reassess contraindications and collect data on adult and pediatric patients with multiple comorbidities who are often excluded from RCTs. AIT is the sole disease-modifying therapeutic approach capable of inducing tolerance and offering a long-term response to allergens. AIT has been shown to play a role in arresting the 'allergic march' in young people, which reduces the risk of developing asthmatic clinical manifestations. Although RCTs are considered the gold standard for evaluating the efficacy and safety of AIT, their duration is usually too short (seldom lasting more than 1 year) to assess the long-term effects of AIT. Several long-term studies show that AIT's effect depends strongly on its use duration.

Application of PLGA-PEG-PLGA Nanoparticles to Percutaneous Immunotherapy for Food Allergy.

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies.

Monitoring and stopping Hymenoptera venom immunotherapy: Contribution of IgE blocking activity

BackgroundHymenoptera venom allergy involves strong public health issues and has an undeniable impact on quality of life. Allergen immunotherapy (AIT) has shown a long-term efficacy in this severe and potentially lethal allergy. However, no biomarker can predict the effectiveness of this treatment. ObjectivesWe evaluate the contribution of IgE blocking activity, a functional biomarker carried out in our center using flow cytometry, to predict the efficacy of AIT. MethodsThis retrospective study from 1985 to 2022 describes in detail the demographic, clinical and biological characteristics of patients who benefited from AIT with Hymenoptera venom at the University Hospital of Limoges. The outcome measure used was the presence of anaphylactic reaction (Grade I to IV according to Ring and Messmer) in case of a new sting after discontinuation of AIT. ResultsOur study, mainly composed of patients allergic to Vespula wasp, did not emphasize the interest of IgE blocking activity in the prediction of a relapse after a new sting. However, this inhibition showed a significant correlation with the amount of IgG4 antibodies. ConclusionThere is no biomarker that can helps decision of stopping allergen immunotherapy. However, low levels of IgE blocking activity may suggest a likelihood of relapse. sIgG4, in correlation with IgE blocking activity, could be useful for monitoring treatment response. Additional studies are necessary to gain a thorough understanding of the composition of inhibitory antibodies.

Allergen immunotherapy adverse events in adults with respiratory allergies-data from ADER: An EAACI task force report.

Registries can yield important insights on allergen immunotherapy (AIT) outcomes in daily clinical practice. However, systematic recordings of adverse events (AE) due to AIT in real-life are lacking. The Allergen Immunotherapy Adverse Events Registry (ADER) is a prospective, multicenter registry on real-life AIT safety. Data on adults (>18 years old) with respiratory allergies receiving AIT with mites, pollens, epithelia, and/or molds were retrieved and analyzed from ADER. The frequency, characteristics and risk factors of AE were investigated. The MedDRA terminology was used to record AE. A total of 1545 individuals with a mean age of 33 ± 10 years receiving 1815 AIT courses (n = 1060 sublingual (SLIT); n = 755 subcutaneous (SCIT)) in centers from eight countries were included. Patients had allergic rhinitis (65%) or, asthma only (3.7%) or rhinitis with asthma (31.2%). Grass was the most frequent specific sensitizer (60.7%), followed by mites (45.5%), birch pollen (20.6%), epithelia (16.1%), and molds (8%). There were 296 AE recorded in 115 patients (7.4%). A higher frequency of AE occurred during up-dosing (59%) compared to maintenance. Severe reactions were rare (0.2%), all in the context of SCIT. After 6 weeks of maintenance only one moderate AE was recorded. The most frequently reported symptoms were from the respiratory system and the skin. Having asthma, doing SCIT, AIT with mugwort, cat, or birch were associated with higher risk for AE while the use of allergoids induced lower risk. In real life clinical practice, AIT-associated AE occur in a minority of patients, while severe reactions are rare. The presence of asthma and use of SCIT are risk factors, while the use of modified allergens lowers the risk.

Allergen immunotherapy in patients with atopic dermatitis allergic to house dust mite: A systematic review and meta-analysis.

Allergen immunotherapy in patients with atopic dermatitis allergic to house dust mite: A systematic review and meta-analysis.

In Silico Identification of Peanut Peptides Suitable for Allergy Immunotherapy in HLA-DRB1*03:01-Restricted Patients.

Peanut allergy, a prevalent and potentially severe condition affecting millions worldwide, has been linked to specific human leukocyte antigens (HLAs), suggesting increased susceptibility. Employing an immunoinformatic strategy, we developed a "logo model" based on amino acid frequencies in the peptide binding core and used it to predict peptides originating from 28 known peanut allergens binding to HLA-DRB1*03:01, one of the susceptibility alleles. These peptides hold promise for immunotherapy in HLA-DRB1*03:01 carriers, offering reduced allergenicity compared to whole proteins. By targeting essential epitopes, immunotherapy can modulate immune responses with minimal risk of severe reactions. This precise approach could induce immune tolerance with fewer adverse effects, presenting a safer and more effective treatment for peanut allergy and other allergic conditions.

Otolaryngic Allergy Patient Journey Mapping: A Framework for Allergy Immunotherapy Adherence.

Allergen-specific immunotherapy (AIT) is an effective treatment for allergic disease but requires long treatment duration and premature cessation is of significant concern. Drivers of premature cessation remain poorly understood and no predictive models currently exist. We hypothesized that a novel patient journey map and de novo real-time patient electronic health status instruments (eHSIs) could effectively capture patient perceived cost, commitment, and treatment benefit to identify individual patients at risk for premature AIT cessation. Cross-Sectional Observational Study. A single Otolaryngology allergy immunotherapy (AIT) program was studied over 5 years. Instances of premature cessation were classified. An Otolaryngic Allergy Patient Journey Map was developed to identify and target automated, real-time, patient-reported, electronic health status instrument responses. Data capture was robust, with 61,406 data points collected and an eHSI survey completion rate of 81.3%. However, based on correlation analysis and logistic regression alone, real-time eHSI responses were not predictive of individual patient premature AIT cessation. A total of 597 AIT patients discontinued treatment prematurely: 64.4% stopping within the first year. Specifically, 74.0%-76.3% of subcutaneous AIT patients and 88.5%-100% of sublingual AIT patients did not complete the minimum recommended treatment duration of 3 years. Patient journey mapping can aid in the design of longitudinal care models and patient engagement strategies. Yet, eHSI patient responses of perception of AIT cost, benefit, and convenience did not correlate with the likelihood of premature treatment cessation. Our imperfect clinical intuition may not account for the dynamic drivers of premature AIT discontinuation. Future development of predictive tools feed by large patient-centric data sets may be incorporated into routine practice resulting in delivery of a more streamlined and personalized approach with reduced premature AIT cessation, improved outcomes, and reduced health care expenditures. NA Laryngoscope, 2024.

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.