Allergen Immunotherapy Research Articles

Allergen-Specific Immunotherapy and Trained Immunity.

The high prevalence of allergic diseases reached over the last years is attributed to the complex interplay of genetic factors, lifestyle changes, and environmental exposome. Allergen-specific immunotherapy (AIT) is the single therapeutic strategy for allergic diseases with the potential capacity to modify the course of the disease. Our knowledge of the mechanisms involved in allergy and successful AIT has significantly improved. Recent findings indicate that long-term allergen tolerance upon AIT discontinuation not only relies on the generation of proper adaptive immune responses by the generation of allergen-specific regulatory T and B cells enabling the induction of different isotypes of blocking antibodies but also relies on the restoration of proper innate immune responses. Trained immunity (TRIM) is the process by which innate immune cells acquire memory by mechanisms depending on metabolic and epigenetic reprogramming, thus conferring the host with increased broad protection against infection. This concept was initially explored for infectious diseases, as well as for vaccination against infections, but compelling experimental evidence suggests that TRIM might also play a role in allergy and AIT. Hyperinflammatory innate immune responses in early life, likely due to TRIM maladaptations, lead to aberrant type 2 inflammation-enhancing allergy. However, exposure to farming environments and specific microbes prevents recurrent infections and allergy development, likely due to mechanisms partially depending on TRIM. TRIM-based vaccines and next-generation AIT vaccines inducing metabolic and epigenetic reprogramming in innate immune cells and their precursors have shown protective antiallergic effects. A better understanding of the factors involved in early-life TRIM mechanisms in the context of allergy and the identification and characterization of novel tolerance inducers might well enable the design of alternative TRIM-based allergen vaccines for allergic diseases.

The Role of Immunotherapy in the Management of Food Allergy

Food allergy is a health disorder that results from a specific immune response to food. According to the World Allergy Organisation (WAO), 22% of the world's population suffers from allergies, and this number is increasing every year. The increasing morbidity and mortality rates of food allergy cases highlight the need for accurate diagnosis and appropriate treatment. Advances in science and technology have enabled a paradigm shift in allergy prevention, moving from allergen avoidance to desensitisation and active induction of immunological tolerance (immunotherapy). Immunotherapy for food allergy can utilise various routes of administration, including subcutaneous (SCIT), oral (OIT), sublingual (SLIT), intralymphatic (ILIT), and epicutaneous (EPIT). Currently, there are newer formulation approaches that modify the activity of the allergen, improving safety while maintaining effectiveness. The principle of immunotherapy involves gradually increasing exposure to specific allergens, resulting in desensitisation or increased tolerance to these allergens. This article aims to determine the role of immunotherapy in the management of food allergy. Keywords: Food Allergy, Immunotherapy, Desentization

Allergen immunotherapy in children and adolescents: current aspects 2024

SummaryAllergen immunotherapy (AIT) is a proven treatment for allergic diseases such as allergic rhinoconjunctivitis (ARC), allergic asthma (AA) and insect sting allergy. Particularly in children and adolescents, who have a high prevalence of these diseases, AIT plays a crucial role in not only alleviating symptoms but also influencing the natural course of the disease. This article examines the use and importance of AIT in children and adolescents in Germany in the final phase of the Therapy Allergen Ordinance (TAV). The focus is on the efficacy and safety of the therapy, as well as the approval of the respective therapeutic allergens for the respective age group.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

Survey on Treatment-Seeking Patterns in Patients With Allergic Rhinitis

Background and Objectives: The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments.Methods: In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments.Results: We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied).Conclusion: Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.

Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses. Here we apply a multilayer-omics approach to reveal dynamic peripheral immune landscapes during the AIT-initiation phase in venom allergy patients (VAP) versus pollen-allergic and healthy controls. Already at baseline, VAP exhibit altered abundances of several cell types, including classical monocytes (cMono), CD4+ hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) and CD8+ counterparts (Tc1-Tc17 or Tc1/17). At 8-24 h following AIT launch in VAP, we identify a uniform AIT-elicited pulse of late-transitional/IL-10-producing B cells, IL-6 signaling within Th2 cells and non-inflammatory serum-IL-6 levels. Sequential induction of activation and survival protein markers also immediately occur. A disequilibrium between serum IL-6 and cMono in VAP baseline is restored at day seven following AIT launch. Our longitudinal analysis discovers molecular switches during initiation-phase insect-venom AIT that secure long-term outcomes. Trial number: NCT02931955.

The use and implementation of omalizumab as food allergy treatment: Consensus-based guidance and Work Group Report of the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology.

Omalizumab was recently approved by the US Food and Drug Administration for treatment of any single food allergy or multiple food allergies in children aged 1 year and older and adults. There is currently no formal guidance regarding recommended best practices for omalizumab use in food allergy, including patient selection, anticipated goals and outcomes of therapy, procedure for monitoring patients who elect to start omalizumab therapy, and ways in which omalizumab can be incorporated into the landscape of food allergy management and daily clinical practice. This work group report was developed by the food allergy therapies subcommittee of the Adverse Reactions to Foods Committee within the American Academy of Allergy, Asthma & Immunology. Consensus, evidence-based guidance regarding experts' recommendations for using omalizumab to treat children and adults with food allergy was developed by using modified Delphi methodology. In iterative fashion, a total of 8 statements regarding how to use omalizumab to treat patients with food allergy were developed by 16 clinical experts. This guidance provides the clinician with a suggested approach to patient selection, initiation of therapy, monitoring of efficacy, and long-term follow-up care. The role of preference-sensitive care is emphasized, with most statements offering care recommendations relevant to the culture and values of a particular practice setting.

Master Clinician: How I Counsel a Family Who Is Considering Food Allergy Therapy

Master Clinician: How I Counsel a Family Who Is Considering Food Allergy Therapy

Safety of oral immunotherapy for cashew nut and peanut allergy in children - a retrospective single-centre study.

Oral immunotherapy (OIT) is increasingly used for the treatment of childhood food allergies, with limited data available on cashew nut OIT. This real-life study investigated the safety and feasibility of cashew nut OIT, comparing it with peanut OIT, with a focus on the up-dosing process. We analysed cashew nut (n = 24) and peanut (n = 38) OIT cases with treatment initiated between 2018 and 2022 at the University Children's Hospital Basel. All patients who commenced therapy within this time frame were enrolled without prior selection. Two different starting protocols were used. Within the up-dosing protocol, the nut intake was incrementally increased by 20-30% every 2 weeks until reaching a maintenance dose of 1 g of nut protein. After consuming the maintenance dose regularly for 18-24 months, a second oral food challenge was performed. Patients who passed this challenge were considered desensitised. The safety of the therapy was evaluated based on the severity of adverse reactions during the up-dosing phase. Symptom severity was evaluated using the validated ordinal food allergy severity scale (o-FASS-5). Over the study period, 33% of cashew nut-allergic and 63% of peanut-allergic patients experienced mild to moderate allergic reactions. Severe allergic reactions occurred in five peanut-allergic children with high baseline allergen-specific IgE levels. Six patients with peanut, and none with cashew nut OIT, discontinued the therapy due to adverse reactions. The mean duration to reach the maintenance phase was longer for children with asthma or another food allergy. Among children who already underwent the second oral food challenge, desensitisation was achieved in 91% (11 out of 12) of cashew nut- and 73% (11 out of 15) of peanut-allergic patients. Cashew nut OIT had a low severity of adverse reactions and was generally well-tolerated. However, patient characteristics influenced side effect risk and treatment duration, emphasising the need for individualised OIT strategies.

Adjuvant alum regulates the eIF2a-GATA3 axis in CD4+ T cells to influence allergen immunotherapy.

Allergen-specific immunotherapy (AIT) is an aetiology-targeting therapy for allergic diseases. The therapeutic mechanism of AIT is not fully understood yet. Endoplasmic reticulum stress is associated with the pathogenesis of allergic disorders. This study aims to elucidate the effects of AIT on suppressing allergic response through regulating endoplasmic reticulum stress. In this study, patients with perennial allergic rhinitis were recruited. AIT was conducted for the patients. An allergic rhinitis (AR) mouse model was established with mite extracts as allergens. We found that AIT modulated the endoplasmic reticulum stress status in peripheral CD4+ T cells in patients with allergic rhinitis. The intensity of endoplasmic reticulum stress associated the PERK (protein kinase RNA-like endoplasmic reticulum kinase)-eIF2a (eukaryotic translation initiation factor 2a) axis in CD4+ T cells was upregulated by AIT, which was closely associated with the improvement in allergic rhinitis response after AIT. eIF2a interacted with GATA3 to downregulate the IL4 gene transcription in CD4+ T cells. High doses of aluminium hydroxide (alum) in AIT vaccines enhanced the activity of XBP1 to suppress eIF2a in CD4+ T cells. AIT containing a low dose of alum effectively mitigated the experimental allergic rhinitis, while the AIT without alum or a high dose of alum exacerbated the experimental allergic rhinitis. In conclusion, the alum adjuvant in allergen vaccines can regulate the activity of eIF2a to regulate the expression of Th2 cytokines in CD4+ T cells. Manipulating the alum dose in AIT vaccines has the potential to enhance the therapeutic effects of AIT.

A RELATION BETWEEN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS (CRSwNP) AND COVID-19 COURSE

Abstract The data on impact of chronic rhinosinusitis (CRS) on SARS-CoV-2 virus susceptibility and COVID-19 course were reviewed. CRS heterogeneity is determined by different types of inflammatory response. A heterogeneous CRS is divided into CRS without polyps and with nasal polyps (CRSwNP) is accounted for by diverse underlying immune responses. Hypersecretion of interleukins (IL)-4, IL-5, IL-13 in eosinophilic CRSwNP downmodulates angiotensin-converting enzyme (ACE)-2 receptor expression that should reduce SARS-CoV-2 infection risk because ACE2 is a main cellular tropism factor for SARS-CoV-2. In neutrophilic CRS type 1 immune response predominates, with activation of Th-1 cells, hypersecretion of interferon (IFN)-γ and tumor necrosis factor (TNF)-α to increase ACE2 expression. However, another data also show that hypoxemia level and pulmonary system damage did not differ between patients with CRS and CRS without polyps. Literature contradictions may be related to differences in availability of medical care, treatment of bronchial asthma (BA) as well as coverage of PCR testing. Regarding use of local or systemic glucocorticosteroids (GCS) effect on SARS-CoV-2 infection risk, some authors believe that GCS may increase COVID-19 severity and mortality, probably by downmodulating local innate immune response factors. According to other data, GCS may reduce ACE2 expression, or there is no relationship between previous GCS use, the incidence of COVID-19 and the frequency of treatment in the intensive care unit. Biological therapy of CRSwNP and BA with monoclonal antibodies did not aggravate COVID-19 severity and mortality risk. Although such data are currently limited, authors recommend not to interrupt such treatment during the epidemic, as well as continue taking leukotriene receptor blockers that can further inhibit major protease (Mpro) of the SARS-CoV-2 virus. However, according to international guidelines on COVID-19 treatment, using CRSwNP and asthma biological therapy should be discontinued until the patients recover completely. Allergen-specific immunotherapy (ASIT) should be interrupted in the case of confirmed COVID-19 due to a probability of developing severe COVID-19. After COVID-19, disturbances in the immune system may persist and possibly change the course of CRS, therefore requiring to modify therapeutic approaches for such patients. At the same time, the worldwide literature has been gradually accumulating information on pathogenesis underlying alterations in such patients including those with CRS, which requires development of new therapeutic approaches.

One-strength dose escalation of house dust mite depot product for subcutaneous immunotherapy is safe and tolerable.

Allergen immunotherapy (AIT) aims at modulating the immune response by administration of allergen preparations at regular intervals over several years (1). For subcutaneous AIT (SCIT), the treatment is initiated with a dose escalation phase followed by a maintenance dose administration. Over the last decade, there has been a trend towards shortening dose escalation regimens to increase patient adherence. This open-label, phase II trial aimed to investigate the safety and tolerability of a house dust mites (HDMs) SCIT product when used in a newly designed one-strength dose escalation scheme. Patients, aged 12-65, suffering from HDM-allergic rhinitis/rhinoconjunctivitis ± asthma were included. Patients were randomized to the one-strength (6 injections from the highest strength 3) or the Standard dose escalation regimen (14 injections from strengths 1 to 3) using the HDMs-SCIT product. All adverse events were reported. Tolerability was assessed on the Likert scale. One hundred and forty-three patients were randomized, 79 adults and 64 adolescents. In total, the one-strength regimen caused more adverse drug reactions (ADRs) than the Standard regimen (p = .0457). With both regimens most ADRs were local reactions which occurred more often in the one-strength group (p = .0393). But there was no significant difference in the number of patients affected by systemic or serious ADRs between both regimens. No relevant differences occurred between the two age groups and no other risks were observed for adolescents compared to adults. The safety and tolerability of both regimens can be considered comparable, as most ADRs were local reactions, primarily rated as mild in intensity. Nevertheless, the one-strength regimen caused more ADRs. Reducing the number of injections from 14 to 6 while using only one strength offers the potential to improve patient adherence which further might increase clinical efficacy. Future trials could confirm this hypothesis.

Novel Approaches to Allergen Immunotherapy for Respiratory Allergies.

Allergen immunotherapy (AIT) remains the cornerstone for managing respiratory allergies, offering long-term symptom relief, disease modification, and prevention of disease progression. While novel approaches like intralymphatic and epicutaneous immunotherapy and the combination of allergens with adjuvants show promise, traditional methods remain effective and safe. Hypoallergenic T-cell peptide vaccines and recombinant allergens require further research to confirm their clinical benefits. Passive immunotherapy, while demonstrating effectiveness in specific cases, needs exploration of its long-term efficacy and broader applicability. Combining AIT with biologics may enhance safety and treatment outcomes. Despite emerging innovations, allergen-specific immunotherapy with natural allergen extracts remains the primary disease-modifying treatment, offering long-term symptom relief and prevention of disease progression. Continued research is essential to refine and optimize allergen immunotherapy strategies, providing patients with more effective and personalized treatment options.

Allergen-specific sublingual immunotherapy altered gut microbiota in patients with allergic rhinitis.

Allergen-specific immunotherapy (AIT) induces long-term immune tolerance to allergens and is effective for treating allergic rhinitis (AR). However, the impact of sublingual immunotherapy (SLIT) on gut microbiota from AR patients and its correlation with treatment efficacy remains unclear. In the present study, we enrolled 24 AR patients sensitized to Dermatophagoides farinae (Der-f) and 6 healthy donors (HD). All AR patients received SLIT treatment using standardized Der-f drops. Stool samples were collected from AR patients before treatment, and 1- and 3-months post-treatment, as well as from HD, for metagenomic sequencing analysis. AR patients had significantly lower richness and diversity in gut microbiota compared to HD, with notable alterations in composition and function. Besides, three months post-SLIT treatment, significant changes in gut microbiota composition at the genus and species levels were observed in AR patients. Streptococcus parasanguinis_B and Streptococcus parasanguinis, which were significantly lower in AR patients compared to HD, increased notably after three months of treatment. LEfSe analysis identified these species as markers distinguishing HD from AR patients and AR patients pre- from post-SLIT treatment. Furthermore, changes in the relative abundance of S. parasanguinis_B were negatively correlated with changes in VAS scores but positively correlated with changes in RCAT scores, suggesting a positive correlation with effective SLIT treatment. SLIT treatment significantly alters the gut microbiota of AR patients, with S. parasanguinis_B potentially linked to its effectiveness. This study offers insights into SLIT mechanisms and suggests that specific strains may serve as biomarkers for predicting SLIT efficacy and as modulators for improving SLIT efficacy.

A narrative review on allergy and exposure to domestic and non-domestic animals: favorable and unfavorable effects.

The aim of this contribution was to highlight the "favorable" and "unfavorable" roles of domestic and non-domestic animals on airway sensitization processes and on the type/severity of the clinical symptoms induced by their exposure. We performed a literature research in MEDLINE for allergic manifestations and animals. Pets can be "allergy friends" through mechanisms related to hygiene hypothesis and translational aspects, the dual role of IgG4 antibodies for pets, and their promising role as healthcare service animals (dogs). On the contrary, animals can be "allergy enemies" when inducing allergic sensitization and respiratory symptoms (sometimes leading to severe reactions), and also due to cross reactivity with other pets allergens, indirect exposure and ubiquity of their allergens, cross reactivity between Can f 5 and human prostate-specific antigen (PSA). Moreover, in some cases they can trigger anaphylaxis, induce occupational asthma, and act as pests. Finally, we must outline the modest efficacy of allergen immunotherapy (AIT) for their allergens. From a strictly allergological perspective, it is evident that the "negative" aspects resulting from exposure to domestic / non-domestic animals outweigh the "positive" aspects. As a consequence, it is up to humans to seek new ways to balance the pros and cons by exploring research areas that can allow the best possible coexistence with subjects at risk of allergy with domestic and non-domestic animals.

Mechanism differences in the start time of sublingual immunotherapy in a mouse allergic airway inflammation model

Sublingual immunotherapy (SLIT) has received considerable attention as a method for allergen immunotherapy (AIT). However, the mechanism of SLIT, especially its timing, has not been thoroughly investigated. We evaluated therapeutic and prophylactic SLIT in an allergic airway inflammation model and evaluated their efficacies. Mice were intranasally exposed to Dermatophagoides farinae (Der f) extract and received SLIT before (prophylactic model) and after (therapeutic model) intranasal exposure of Der f. We investigated airway responsiveness, airway inflammation, allergen-specific antibodies, lung histology and single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing were also investigated. SLIT in the therapeutic model was effective; however, the effects of SLIT in the prophylactic model were stronger and immune tolerance was maintained for three months. ScRNA-seq of lung CD4+CD25+ T cells revealed that the expansion of induced T regulatory (iTreg) cells was greater in the prophylactic model than that in the therapeutic model. Additionally, the TCR repertoire of iTregs from the prophylactic model was abundant, sharing many clones with the TCR repertoire of effector T cells. These data suggest that the prophylactic model of AIT is extremely effective and persistent, and may respond to allergen diversity, and provide evidence for the clinical recommendation of preventive AIT.

Application of Nanoparticles for Immunotherapy of Allergic Rhinitis.

Allergen Immunotherapy (AIT) is the only etiological therapeutic method available for allergic rhinitis (AR). Currently, several options for AIT in the market, such as subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), have different routes of administration. These traditional methods have achieved encouraging outcomes in clinic. However, the side effects associated with these methods have raised the need for innovative approaches for AIT that improve safety, shorten the course of treatment and increase local drug concentration. Nanoparticles (NPs) are particles ranging in size from 1 to 100 nm, which have been hired as potential adjuvants for AIT. NPs can be employed as agents for modulating immune responses in AR or/and carriers for loading proteins, peptides or DNA molecules. This review focuses on different kinds of nanoparticle delivery systems, including chitosan nanoparticles, exosomes, metal nanoparticles, and viral nanoparticles. We summarized the advantages and limitations of NPs for the treatment of allergic rhinitis. Overall, NPs are expected to be a therapeutic option for AR, which requires more in-depth studies and long-term therapeutic validation.

An International Delphi Consensus on the Management of Pollen-Food Allergy Syndrome: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee

Pollen-food-allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable. To develop consensus recommendation statements for managing patients with PFAS. An international panel of allergists, researchers, and nutritionists with an interest in PFAS from 25 different institutions across 11 countries convened and a list of statements was written by 3 authors. The RAND/University of California Los Angeles methodology was adopted to establish consensus on the statements. After 2 Delphi rounds, a consensus was reached on 14 statements. The panel agreed that patients with PFAS would benefit from counseling on the nature and basis of PFAS and the rare chance of more severe systemic reactions and their recognition. The panel agreed on avoiding the raw food responsible for the index reaction, but not potentially cross-reactive fruits/vegetables based on the responsible food of the index reaction. Epinephrine autoinjectors should be recommended for patients with PFAS who experienced severe symptoms (beyond the oropharynx) or for patients considered at risk for severe reactions. The panel agreed that the benefit of allergen immunotherapy remains unclear and that PFAS should not be considered the primary indication for such intervention. We developed consensus statements regarding counselling patients about the nature and severity of PFAS, potential risk factors, dietary avoidance, epinephrine autoinjector prescription, and allergen immunotherapy consideration for patients with PFAS.

Efficacy and perceived satisfaction of 3-year SLIT in children with allergic rhinitis and asthma: a pilot study.

Despite the presence of robust evidence, there is very limited data on the efficacy of allergen immunotherapy (AIT) for selected patients. Accordingly, we aimed to evaluate the efficacy and perceived satisfaction of a 3-year course of sublingual immunotherapy (SLIT) in a paediatric population with allergic rhinitis and/or asthma. A pilot, monocentre, retrospective cohort study was performed. One hundred fifty-three children who fulfilled the criteria for allergic rhinitis and asthma and were either mono- or poly-sensitized were enrolled. A standardized questionnaire assessing perceived efficacy, use of rescue medication, disease control, number of exacerbations, quality of life, and perceived satisfaction was administered to each patient. Seventy patients (49 males, 21 females; mean age, 14.3±1.9 years) were included in the final analysis. All 70 patients received SLIT for up to 3 years, with 100% adherence to the treatment throughout the study. Significant improvements in symptoms and quality of life were reported (p<0.01). There was also a significant decrease in disease severity, use of rescue medication, and sleep disturbances (p<0.01). Additionally, a significant improvement in school performance was also recorded (p<0.01). Of the enrolled patients, 60 out of 70 (85.7%) reported being very satisfied, 6 out of 70 (8.57%) were much satisfied, and 4 out of 60 (5.71%) were satisfied. We were the first to demonstrate the efficacy and perceived satisfaction of a 3-year SLIT in a paediatric population, with 100% treatment adherence throughout the study.

Management of eosinophilic esophagitis in pediatric patients undergoing oral immunotherapy for food allergies: A two-center case series

Management of eosinophilic esophagitis in pediatric patients undergoing oral immunotherapy for food allergies: A two-center case series