Allergen Immunotherapy Research Articles

Why is pet (cat/dog) allergen immunotherapy (AIT) such a controversial topic? Current perspectives and future directions.

Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals".

Basics in diagnostics and therapy of allergic diseases for ENT consultations

Allergies play a pivotal role in the daily practice of ENT specialists. Allergic symptoms induced by inhalant allergens are widespread in the population and can manifest through a wide range of symptoms, including rhinorrhea, sneezing, conjunctival redness, cough and dyspnea. Inconsistent diagnosis and treatment of allergic conditions can lead to reduced quality of life, decreased work performance, and socioeconomically significant secondary diseases. In addition to the medical history, the skin prick test and serological IgE diagnostics are the most important diagnostic procedure for detecting type-I allergies. To clarify clinical relevance, molecular diagnostics and nasal provocation testing may be employed. The key to effective treatment lies in a comprehensive allergological diagnosis coupled with a detailed patient history. General treatment recommendations such as allergen avoidance and nasal irrigation should complement pharmacological therapy. In the treatment of allergic rhinitis topical steroids are first line treatment options. The primary goal of treatment is symptom control, and if control is insufficient, causal therapy through specific allergen immunotherapy is recommended. Challenges in the ENT clinic involve selecting the necessary diagnostics and appropriate, effective treatments. Hence, using diagnostic and treatment algorithms, as well as standardized patient history questionnaires, can serve as invaluable tools in daily patient interactions, especially considering limited time availability.

Unraveling the Molecular Threads: A Comprehensive Review of the Pathogenesis and Therapeutic Insights Into Allergic Rhinitis.

Allergic rhinitis (AR) is a prevalent inflammatory disorder of the nasal mucosa, triggered by allergen exposure and characterized by symptoms such as sneezing, nasal congestion, itching, and rhinorrhea. This comprehensive review aims to unravel the molecular mechanisms underpinning AR, exploring the pathogenesis from allergen recognition to chronic inflammation and tissue remodelling. Central to the disease are immunoglobulin E (IgE)-mediated hypersensitivity reactions, involving key inflammatory mediators and cellular players such as mast cells, eosinophils, and T cells. Genetic predisposition and environmental factors also play significant roles in susceptibility and disease progression. Therapeutic strategies for AR are varied, ranging from symptomatic relief through antihistamines and nasal corticosteroids to more targeted approaches like allergen-specific immunotherapy. Emerging treatments focus on novel molecular pathways, with a growing emphasis on personalized medicine to optimize patient outcomes. Despite advancements, challenges remain in fully understanding the heterogeneity of AR and developing universally effective treatments. This review synthesizes current knowledge, highlighting critical insights into the molecular basis of AR and their implications for clinical practice. It underscores the need for integrated, multidisciplinary approaches to enhance therapeutic efficacy and calls for ongoing research to address unresolved questions and explore new frontiers in AR management. Through this comprehensive synthesis, the review aims to inform and inspire future research and clinical strategies, ultimately improving the quality of life for individuals affected by AR.

An Overview of Adherence—What It Is and Why It Is Important

Asthma, allergic rhinitis, and food allergy are common allergic diseases, yet adherence to many management options remains poor, leading to worse health outcomes and financial implications for society and health systems. The underlying causes of non-adherence are numerous, ranging from patient specific factors to broader socioeconomic and systems-based factors. In this review, we aim to discuss the definition of adherence, which can be divided into 3 components: initiation, implementation, and persistence, as well as to review various methods of measuring adherence. Subsequently, we will review the epidemiology of adherence to asthma and allergic rhinitis medications, allergen immunotherapy, and oral immunotherapy. Finally, we will discuss the multifaceted etiology of poor adherence and its subsequent impact on patients and society.

A diagnostic approach to IgE-mediated food allergy: A practical algorithm.

A food reaction history is the basis of food allergy diagnoses. Several levels of food allergy diagnostic testing can confirm or refute the presence of food allergy. The choice of food allergy testing modality should be informed by the reaction history and determined by the testing goals. Testing modalities include skin-prick testing, in vitro specific immunoglobulin E testing, component-resolved testing, epitope threshold testing, and basophil activation testing. The goal of food allergy testing may be merely to confirm the diagnosis of food allergy or may be used to guide passive (avoidance) or active (allergen immunotherapy) management. The most appropriate diagnostic path should consider testing predictive value, the goal of the evaluation, patient and family food allergy anxiety, and cost. Peanut allergy testing provides an algorithm for testing pathways.

Clinical and immunological response to sublingual allergen-specific immunotherapy: cumulative dose-response relationship

Clinical and immunological response to sublingual allergen-specific immunotherapy: cumulative dose-response relationship

Allergy therapy for patients with a cardiac channelopathy: Do not withhold lifesaving treatments

Allergy therapy for patients with a cardiac channelopathy: Do not withhold lifesaving treatments

Long-Term Adherence and Risk of Allergic Reactions in Patients Who Attained Milk Oral Immunotherapy Maintenance

BackgroundOral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse. ObjectiveWe aimed to assess the long-term adherence rates to OIT protocol and the associated risk of allergic reactions. MethodsPatients who completed milk OIT and reached a maintenance dose of 200 ml of milk were surveyed biannually on their dairy consumption and occurrence of allergic reactions. A survival analysis was performed to evaluate the association between the risk of reaction and adherence to OIT maintenance protocol. ResultsThe cohort consisted of 50 patients. Only 56% of the cohort adhered to protocol, which consisted of ingesting a minimum of 200 ml of milk at least 3 times per week. Adherent patients had a significantly reduced risk of allergic reactions, as well as a reduced incidence of anaphylaxis, healthcare/ER visits, and epinephrine/antihistamine administration. ConclusionThe findings demonstrate the importance of consistent maintenance dose consumption in the management of food allergies, with regular milk consumption contributing to the maintenance of unresponsiveness and decreased risk of allergic symptoms.

Grass pollen allergoids conjugated with mannan for subcutaneous and sublingual immunotherapy: a dose-finding study.

Polymerized allergoids conjugated with mannan represent a novel approach of allergen immunotherapy targeting dendritic cells. In this study, we aimed to determine the optimal dose of mannan-allergoid conjugates derived from grass pollen (Phleum pratense and Dactylis glomerata) administered via either the subcutaneous or sublingual route. A randomized, double-blind, placebo-controlled trial with a double-dummy design was conducted, involving 162 participants across 12 centers in Spain. Subjects were randomly allocated to one of nine different treatment groups, each receiving either placebo or active treatment at doses of 500, 1,000, 3,000, or 5,000 mTU/mL over four months. Each participant received five subcutaneous (SC) doses of 0.5 mL each, every 30 days, and a daily sublingual (SL) dose of 0.2 mL. Participants who received active treatment through SC, received placebo through SL. Participants who received active treatment through SL, received placebo SC. One Group, as control, received bot SC and SL placebo. The primary efficacy outcome was the improvement in titrated nasal provocation tests (NPT) at the end of the study compared to baseline. Secondary outcomes included specific antibody (IgG4, IgE) and cellular (IL-10 producing and regulatory T cell) responses. All adverse events and side reactions were recorded and assessed. Post-treatment, the active groups showed improvements in NPT ranging from 33% to 53%, with the highest doses showing the greatest improvements regardless of the administration route. In comparison, the placebo group showed a 12% improvement. Significant differences over placebo were observed at doses of 3,000 mTU/mL (p=0.049 for SL, p=0.015 for SC) and 5,000 mTU/mL (p=0.011 for SL, p=0.015 for SC). A dose-dependent increase in IgG4 was observed following SC administration, and an increase in IL-10 producing cells for both routes of administration. No serious systemic or local adverse reactions were recorded, and no adrenaline was required. Grass pollen immunotherapy with mannan-allergoid conjugates was found to be safe and efficacious in achieving the primary outcome, whether administered via the subcutaneous or sublingual routes, at doses of 3,000 and 5,000 mTU/mL. https://www.clinicaltrialsregister.eu/ctr-search (EudraCT), identifier 2014-005471-88; https://www.clinicaltrials.gov, identifier NCT02654223.

Is It Possible to Predict Systemic Adverse Effects in Subcutaneous Allergen Immunotherapy? Single-Center Experience

Introduction: Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey. Methods: The files of 295 patients who had received SCIT were evaluated retrospectively. Results: SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively). Conclusion: Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.

Use of omalizumab and allergen-specific immunotherapy for the treatment of respiratory allergic diseases in children and adults

Allergen-specific immunotherapy is a method of treatment and prevention of respiratory allergic diseases. Carrying it out changes and improves the course of allergic diseases. One of the promising and new approaches is the combination of allergen-specific immunotherapy with one of the biological drugs, omalizumab. Currently, few such studies have been carried out in the world. 14 works were selected from international databases (eLibrary.ru, PubMed, Embase, Cochrane, Web of Science). Their results were analyzed and summarized. The characteristics of these studies and their design are given. The results of the safety and effectiveness of the combined use of allergen-specific treatment and anti-IgE therapy are described. It was shown that in most cases (13 out of 14), omalizumab therapy precedes allergen-specific immunotherapy. However, the duration of combination treatment, drug regimens, and patient monitoring vary significantly. All studies have established a variety of positive effects of the combined use of omalizumab and allergen-specific immunotherapy (improvement of the course of diseases, increased possibility of treatment with allergens, good tolerability of drugs, etc.). These studies are very promising. Their continuation is required. It is necessary to clarify the most rational schemes for the combined use of anti-IgE and allergen-specific immunotherapy.

The feasibility of allergen-specific immunotherapy for bronchial asthma in children with polysensitization

Relevance. There is a shortage of studies that would evaluate the effectiveness of allergen immunotherapy (AIT) in children with bronchial asthma (BA) and polysensitization.The aim of the study: to evaluate AIT effectiveness with house dust mite (HDM) allergens in the treatment of BA in children polysensitized to perennial allergens, based on the dynamics of the symptoms and medications score.Materials and methods. The open prospective controlled study included 36 children aged 9,6 [6,9; 12,3] years (from 6 years 1 months to 14 years 3 months) with moderate atopic asthma (21 children (58%) and mild asthma (15 children (42%) and polysensitization to household allergens. Each patient was observed in the study for 4 years: 1 year of preliminary observation and 3 years of sublingual AIT with D. pteronyssinus and D. farinae (Staloral, Stallergenes Greer, France). For each year of observation, asthma symptoms and medications used were assessed, and the combined Score was calculated. To confirm sensitization, a prick test was performed using a standard method with allergens: house dust, D. pteronyssinus, D. farinae, cat, dog, horse, pillow feather (Biomed, Russia).Results. Over 2 years of AIT, the decrease in the symptom and medication Score was 46,9%, and at the end of 3rd year of therapy, 59,8% (р = 0,0001 from baseline). A decrease in the combined Score exceeding 34.9% compared to baseline was noted in all patients in the study.Conclusion. Sublingual AIT with HDM allergens is highly effective in the treatment of asthma in children with domestic polysensitization, in terms of reducing symptoms of the disease, the need for pharmacotherapy and the combined Score of symptoms and medications. A significant positive effect was registered already from the first year of AIT and continues to increase over subsequent years of therapy.

New possibilities of allergen-specific immunotherapy in relation to the induction of antiviral immunity in patients with bronchial asthma

Relevance. The review examines modern ideas about the immunomodulatory effect of allergen-specific immunotherapy in relation to increasing resistance to infectious pathogens. The information presented will allow clinicians to take a more conscious approach to the process of planning therapy for bronchial asthma, considering allergen-specific immunotherapy not only as a tool for pathogenetic treatment of causally significant sensitization, but also as a tool for immunomodulatory therapy against respiratory viral infections.Purpose of the work: systematization of accumulated experience in order to provide information for the practicing physician.

Experience of allergen-specific immunotherapy in the patient with oral and systemic manifestations of birch pollen allergy

Introduction. Allergy to birch pollen is a common allergic disease. The main allergen of birch pollen is Bet v 1. The Bet v 1 protein structure is the similar to proteins of hazel, alder and elm pollen, as well as fruits proteins (apples, apricots, peaches, cherries) and vegetables ones (carrots, celery). Therefore, children with an allergy to the Bet v 1 protein may experience oral allergy syndrome (OAS) and even anaphylaxis when eating these foods. Allergen-specific immunotherapy (ASIT) is the indication for the pollen allergy treatment.Presentation of the clinical case. A 11 years old child was observed with a diagnosis of bronchial asthma, allergic form, moderate persistent clinical course. Pollinosis. Allergic rhinitis. Allergic conjunctivitis. Allergy to birch pollen (Bet v 1). Cross food hypersensitivity: oral syndrome (PR-10 proteins) and anaphylaxis (hazelnuts, peanuts). Systemic manifestations of pollen allergy limit immunotherapy due to the possible development of adverse reactions.The child was prescribed sublingual immunotherapy (SLIT) with the medication “Staloral birch pollen allergen”. Baseline therapy was chosen for the child to achieve control of asthma and rhinitis, a hypoallergenic diet with the exclusion of significant food allergens was prescribed. Asthma and rhinitis exacerbation and OAS was observed during the 1st and 2nd treatment courses. Against the background of baseline therapy, SLIT was continued. The full maintenance dose was achieved during the 3rd SLIT course. Immunotherapy contributed to the reduction of symptoms of rhinitis and asthma, reduction of disease clinical course severity, reduction of baseline medications doses and OAS relief.

Features of the course of pollen allergy in children in the Nizhny Novgorod region

Due to its widespread distribution, the problem of pollen allergy does not lose its relevance for practical healthcare: the variety of clinical forms, the possibility of polyvalent sensitization and pathogenetic treatment in the form of allergen-specific immunotherapy determine the importance of studying its clinical and epidemiological features.Materials and methods. A retrospective analysis of 119 discharge summaries of children with diagnoses of “Allergic rhinoconjunctivitis”, “Bronchial asthma”, “Atopic dermatitis”, occurring with clinically significant pollen sensitization, was carried out in the period 2015–2022. The prevalence, clinical features, prevailing symptoms and atopic comorbidity of patients with pollen allergy living in the Nizhny Novgorod region were assessed.Results. Pollen allergy is characterized by a variety of clinical manifestations, which are mainly represented by allergic rhinoconjunctivitis, bronchial asthma, and oral allergic syndrome. In the study, in the majority of patients, polyvalent sensitization was combined with a pronounced variety of products that provoke oral allergic syndrome. Manifestations of pollen allergies requiring seeking medical help are equally distributed among residents of Nizhny Novgorod and the region’s villages.Conclusions. Clinical and epidemiological features of the course of pollen allergy are of great interest to the practicing physician. The variety of manifestations of pollen allergies determines the need for a clinically effective treatment method, which today is ASIT. One of the needs of modern healthcare is to increase the awareness of primary care physicians about atopic diseases, incl. pollen allergy, with the aim of timely referral of patients to a specialist. Currently, allergen-specific immunotherapy is the most effective method of treating manifestations of pollen allergies.

Evolution of standardization of therapeutic and diagnostic allergens produced in Russia

Allergen-specific immunotherapy is based on the development of induced tolerance in patients. Natural extracts are most often used as therapeutic allergens worldwide.The article presents new approaches to biological standardization of subcutaneous administered allergens. It is established that own standard allergens have specific allergenic activity, which was determined on sensitized patients-volunteers. The Russian Federation uses its own units — EAA (Units of Allergenic Activity). 100 000 EAA/mL corresponds to the size of wheal in prick test equal to 8 mm. The internal reference material (RM) of allergenic activity of pollen allergens ”Microgen“ have different specific activity depending on the type of allergen. The most common series have allergenic (specific) activity in the range of 150,000 — 200,000 EAA/mL.The control of the specific activity of allergen drugs is carried out in accordance with the current certified standard samples of the company’s standards. A method of competitive enzyme-linked immunosorbent assay using specific sera containing specific IgE antibodies is used for this purpose.In addition, the specific activity of allergen preparations is certified through three additional characteristics: total protein content (using the Bradford method), protein profile (through electrophoresis in a polyacrylamide gel with sodium dodecyl sulfate under reducing conditions), and authenticity through the presence of major specific components, which is determined by the Western blot method using sera containing IgE antibodies specific for the corresponding allergen.Currently, in the Russian Federation, the standardization of therapeutic and diagnostic allergens is conducted simultaneously according to two indicators: protein nitrogen content, expressed in Protein Nitrogen Units (PNU), and allergenic (specific) activity expressed in units of allergenic activity per milliliter (EAA/ml). While the PNU indicator partially reflects the allergenic properties of the drug, it does not fully capture these properties, making it necessary to remove PNU from the list of quality indicators for allergen medicines. This would require changes to regulatory documentation and instructions for allergens.When evaluating the allergenic activity of allergens, it is now recommended to focus on units of EAA. The consistency of the protein composition and presentation in the drug ensures increased safety and efficacy of therapy, as well as allows for comparison between drugs.

Local manifestations of cross food allergy in children with clinical symptoms of respiratory allergy to birch pollen: solutions

Introduction. According to modern data, Oral Allergy Syndrome (OAS) is most often formed by patients sensitized to the birch family: up to 73% of patients allergic to birch experienced OAS. 86% of them experience their oral symptoms year-round, which significantly affects the quality of life of these patients. The effectiveness of AIT in the treatment of respiratory allergy symptoms is beyond doubt, while the effect on the manifestations of cross-food allergies requires additional study.Objective. To study the clinical effectiveness of the formation of oral tolerance to fruits and vegetables under the influence of allergen-specific immunotherapy (ASIT) with the allergen Staloral® “Birch pollen allergen” (Stallergenes Greer, France).Material and methods. The study (prospective open comparative longitudinal) included 184 patients with respiratory allergy to birch pollen aged 5 to 16 years with confirmed sensitization to the major molecule (Bet v 1). Children of the main group (n = 134, 7.0 [5.0; 9.0] years) had OAS. Children from the comparison group (n = 50, 7.0 [6.0; 10.0] years) did not have OAS. A clinical examination, general clinical and allergological examinations were carried out for each child. Component allergy diagnostics was performed using a multiplex panel (ISAC-112, ImmunoCAP) for children with OAS (n = 40) who had multiple manifestations of cross-food allergies. Patients of both groups (n = 184) received a three-year course of AIT with the allergen Staloral® “Birch pollen allergen”.Results. In patients with OAS, it was possible to achieve the formation of oral tolerance (total or partial) to fresh vegetables and fruits in 88.81% (n = 119, p = 0.000). There was a decrease in the intensity and duration of respiratory allergy symptoms during the pollination season, and the need for pharmacotherapy after a three-year course of AIT Staloral® “Birch pollen allergen” in children of both groups.Conclusions: three-year AIT with the allergen Staloral® “Birch pollen allergen” is able to form oral tolerance in children with cross food allergies to PR-10 proteins of vegetables and fruits.

Local side effects during sublingual allergen-specific immunotherapy and pathogenetically based methods for their correction (Review)

Introduction. The study of the effectiveness and safety of allergen-specific immunotherapy remains relevant due to the emergence of a personalized approach in allergology and new dosage forms. Adverse reactions during sublingual allergen-specific immunotherapy are the leading reason of treatment discontinuation. Understanding the mechanisms of side effects and knowing how to overcome them allows us to achieve better tolerability of allergen-specific immunotherapy and maintain patient compliance.The aim of the review is to combine the available literature data on the frequency, nature, and pathogenetic basis of adverse events during sublingual allergen-specific immunotherapy and to consider options for their prevention and treatment.

The state of allergen-specific immunotherapy in Russia

.

Pearls for practice from the 2023 allergy immunology joint task force on practice parameters GRADE and institute of medicine based atopic dermatitis guidelines.

To review the updated 2023 Allergy Immunology Joint Task Force on Practice Parameters (JTFPP) GRADE and Institute of Medicine (IOM) Based Guidelines for the management of atopic dermatitis. Topical corticosteroids and/or calcineurin inhibitors are recommended in individuals with atopic dermatitis refractory to moisturizer alone and may be used to maintain remission after acute flare control is achieved. Calcineurin inhibitors are a class of immunosuppressants used to effectively manage different autoimmune disorders. Bleach baths and allergen immunotherapy may be beneficial for individuals with moderate-to-severe disease, while elimination diets, azathioprine, methotrexate, mycophenolate, and systemic corticosteroids are not recommended. Dupilumab is strongly recommended for refractory atopic dermatitis. Oral Janus kinase (JAK) inhibitors carry significant risks; however, this class of medicines may be considered in cases of severe or refractory atopic dermatitis with intolerance to dupilumab. Patient preferences regarding cost, availability, feasibility, and tolerability should be integrated into all treatment plans using a shared decision-making approach. The 2023 JTFPP Atopic Dermatitis Guidelines offer up-to-date guidance for the management of atopic dermatitis of varying severity in infants, children, and adults.