[Feeling analysis on allergen immunotherapy on Twitter using an unsupervised machine learning model]. / Análisis de sentimientos acerca de la inmunoterapia con alérgenos en Twitter mediante un modelo de aprendizaje automático no supervisado.

OBJECTIVE: Analyze feelings about allergen-specific immunotherapy on Twitter using the VADER model VADER (Valence Aware Dictionary and sEntiment Reasoner) model. METHODS: tweets related to specific allergen immunotherapy were obtained through the Twitter Application Programming Interface (API). The keywords "allergy shot" were used between January 1, 2012, and December 31, 2022. The data was processed by removing URLs, usernames, hashtags, multiple spaces, and duplicate tweets. Subsequently, a sentiment analysis was performed using the VADER model. RESULTS: A total of 34,711 tweets were retrieved, of which 1928 were eliminated. Of the remaining 32,783 tweets, 32.41% expressed a negative sentiment, 31.11% expressed a neutral sentiment, and 36.47% expressed a positive sentiment, with an average polarity of 0.02751 (neutral) over the 11-year period. CONCLUSIONS: The average polarity of tweets about allergen-specific immunotherapy is neutral over the 11 years analyzed. There was an annual increase in the average polarity over the years, with 2017, 2018, and 2022 having positive polarity averages. Additionally, the number of tweets decreased over time.

OBJETIVO: Analizar los sentimientos acerca de la inmunoterapia alérgeno-específica en Twitter mediante el modelo VADER (Valence Aware Dictionary and sEntiment Reasoner). MÉTODOS: Se utilizaron tweets relacionados con la inmunoterapia alérgeno-específica obtenidos a través del API (Application Programming Interface) de Twitter. Se incorporaron las palabras clave "allergy shot" en el período comprendido entre el 1 de enero de 2012 y el 31 de diciembre de 2022. Los datos obtenidos fueron procesados, eliminando las URL, nombres de usuarios, hashtags, espacios múltiples y tweets duplicados. Posteriormente, se realizó un análisis de sentimientos utilizando el modelo VADER. RESULTADOS: Se recolectaron 34,711 tweets, de los que se eliminaron 1928. De los 32,783 tweets restantes, se encontró que el 32.41% de los usuarios expresó un sentimiento negativo, el 31.11% un sentimiento neutral y el 36.47% un sentimiento positivo, con una media de polaridad de 0.02751 (neutral) a lo largo de los 11 años. CONCLUSIONES: La polaridad media de los tweets acerca de la inmunoterapia alérgeno-específica es neutral a lo largo de los 11 años analizados. Existe un aumento anual en la polaridad media positiva a lo largo de los años, sobre todo entre 2017, 2018 y 2022. La cantidad de tweets disminuyó con el tiempo.

Recombinant T-cell epitope conjugation: A new approach for Dermatophagoides hypoallergen design.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance. Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T-cell epitopes from these three major allergens. METHODS: The hybrid protein termed Der p 2231 containing T-cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. RESULTS: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL- 2, IL-10, IL-15 and IFN-γ, as well as lower levels of IL-4, IL-5, IL-13, TNF-α and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFN-γ and decreased the secretion of IL-4 and IL-5, when compared with parental allergens and D. pteronyssinus extract. CONCLUSIONS: rDer p 2231 has the potential to be used in AIT in patients co-sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T-cells.

Novas perspectivas em imunoterapia: a importância das células dendríticas na imunoterapia alérgeno-específica / New perspectives in immunotherapy: the importance of dendritic cells in allergen-specific immunotherapy

A imunoterapia alérgeno-específica é o único tratamento capaz de alterar o curso natural da doença alérgica. Ensaios clínicos mostram que a imunoterapia é segura e eficaz para muitos pacientes. No entanto, ainda enfrenta problemas relacionados à eficácia, segurança, longa duração do tratamento e baixa adesão dos pacientes. Neste contexto, tem havido intensa pesquisa no desenvolvimento de adjuvantes com objetivo de aumentar a segurança, otimizar os esquemas de tratamento e melhorar a adesão dos pacientes. Alérgenos foram modificados (glicoconjugados) com carboidratos derivados de Saccharomyces cerevisae para aumentar sua captação e apresentação através dos receptores de carboidratos presentes nas células dendríticas, beneficiando-se da capacidade de atuarem na indução de tolerância para iniciar respostas imunes. À luz de novas evidências, essas células constituem alvo terapêutico chave para se obter uma resposta adequada à imunoterapia alérgeno-específica, com potencial de contribuição na inovação do campo da Imunoterapia.

Allergen-specific immunotherapy is the only treatment capable of altering the natural course of allergic disease. Clinical trials have shown that immunotherapy is safe and effective for many patients. However, it still faces problems related to efficacy, safety, long treatment duration and poor patient compliance. In this context, there has been intense research into the development of adjuvant treatments that increase safety, optimize treatment regimens, and improve patient compliance. Allergens were modified (glycoconjugated) with carbohydrates derived from Saccharomyces cerevisae to increase their uptake and presentation through carbohydrate receptors in dendritic cells, benefiting from their ability to induce tolerance and initiate immune response. In light of the new evidence, these cells are a key therapeutic target for adequate response to allergenspecific immunotherapy and can drive innovation in the field of immunotherapy.

Rationally designed hypoallergenic mutant variants of the house dust mite allergen Der p 21.

BACKGROUND: Allergic diseases figure among the most common immune-mediated diseases worldwide, affecting more than 25% of the world's population. Allergic reactions can be triggered by house dust mite (HDM) allergens, of which the so-called group 21 of allergens is considered as clinically relevant. METHODS: Herein, we used a structural bioinformatics and immunoinformatics approach to design hypoallergenic mutant variants of the Der p 21 allergen of Dermatophagoides pteronyssinus, which were then recombinantly expressed in bacteria and tested for their IgE-reactivities. For this, we scanned the wild-type Der p 21 protein for all possible single amino acid substitutions in key IgE-binding regions that could render destabilization of the major epitope regions. RESULTS: Four main substitutions (D82P, K110G, E77G, and E87S) were selected to build mutant variants of the Der p 21 allergen, which were produced in their recombinant forms; two of these variants showed reduced reactivity with IgE. Molecular dynamic simulations and immune simulations demonstrated the overall effects of these mutations on the structural stability of the Der p 21 allergen and on the profile of immune response induced through immunotherapy. CONCLUSIONS: When produced in their recombinant forms, two of the Der p 21 mutant variants, namely proteins K110G and E87S, showed significantly reduced IgE reactivities against sera from HDM-allergic individuals (n = 20; p < 0.001). GENERAL SIGNIFICANCE: This study successfully translated a rational in silico mutagenesis design into low IgE-binding mutant variants of the allergen rDer p 21. These novel hypoallergens are promising to compose next-generation allergen-immunotherapy formulations in near future.

A hybrid of two major Blomia tropicalis allergens as an allergy vaccine candidate.

INTRODUCTION: Allergen-specific immunotherapy (AIT) represents a curative approach for treating allergies. In the tropical and subtropical regions of the world, Blomia tropicalis (Blo t 5 and Blo t 21) is the likely dominant source of indoor allergens. AIM: To generate a hypoallergenic Blo t 5/Blo t 21 hybrid molecule that can treat allergies caused by B tropicalis. METHODS: Using in silico design of B tropicalis hybrid proteins, we chose two hybrid proteins for heterologous expression. Wild-type Blo t 5/Blo t 21 hybrid molecule and a hypoallergenic version, termed BTH1 and BTH2, respectively, were purified by ion exchange and size exclusion chromatography and characterized by physicochemical, as well as in vitro and in vivo immunological, experiments. RESULTS: BTH1, BTH2 and the parental allergens were purified to homogeneity and characterized in detail. BTH2 displayed the lowest IgE reactivity that induced basophil degranulation using sera from allergic rhinitis and asthmatic patients. BTH2 essentially presented the same endolysosomal degradation pattern as the shortened rBlo t 5 and showed a higher resistance towards degradation than the full-length Blo t 5. In vivo immunization of mice with BTH2 led to the production of IgG antibodies that competed with human IgE for allergen binding. Stimulation of splenocytes from BTH2-immunized mice produced higher levels of IL-10 and decreased secretion of IL-4 and IL-5. In addition, BTH2 stimulated T-cell proliferation in PBMCs isolated from allergic patients, with secretion of higher levels of IL-10 and lower levels of IL-5 and IL-13, when compared to parental allergens. CONCLUSIONS AND CLINICAL RELEVANCE: BTH2 is a promising hybrid vaccine candidate for immunotherapy of Blomia allergy. However, further pre-clinical studies addressing its efficacy and safety are needed.

[Allergic rhinitis' treatment in children in Argentina. Update]. / Tratamiento de la rinitis alérgica en pediatría en Argentina. Documento de actualización

Allergic rhinitis (AR) is the most frequent allergic disease. Prevalence in children and teenagers in Argentina ranges between 22.3% and 34.9%. Given this situation, members of the scientific committees of Pediatrics and Rhinitis of the Argentinian Association of Allergy and Clinical Immunology (AAAeIC) have reviewed scientific evidence in order to update the therapeutic regulations of this pathology in the pediatric population. The classification and categorization of AR are currently in full review all around the world. It is necessary to make a differential diagnosis with other non-allergic types of rhinitis in children, and to confirm AR based on the clinical history, physical examination, determination of bio-markers, and/or skin tests. Non-pharmacological treatment includes education and guidelines of environmental control for allergens such as dust mites, anemophilous fungi, animal epithelium, and pollens. Step pharmacological therapy is proposed according to the control of the disease. Second-generation, non-sedating anti-histamines are the first line of therapy. The association with oral decongestants is not recommended in children under 4 years of age. Inhaled corticosteroids are the first choice for both moderate and severe forms. This document warns pediatricians about the importance of an early diagnosis, the rational use of step pharmacological therapy, and specific immunotherapy in children.

La rinitis alérgica (RA) es la enfermedad alérgica más frecuente. La prevalencia en niños y adolescentes de Argentina oscila entre 22.3 y 34.9 %. Ante esto, integrantes de los comités científicos de pediatría y rinitis de la Asociación Argentina de Alergia e Inmunología Clínica (AAAeIC) revisaron evidencia científica para actualizar las normativas terapéuticas de esta patología en la población pediátrica. La clasificación y categorización de la RA se encuentra actualmente en plena revisión en todo el orbe. Es necesario realizar un diagnóstico diferencial con otras rinitis no alérgicas en los niños, y confirmar la RA con base en la historia clínica, el examen físico, la determinación de biomarcadores o pruebas cutáneas. El tratamiento no farmacológico incluye la educación y pautas de control ambiental para alérgenos como ácaros, hongos anemófilos, epitelio de animales y pólenes. Se propone un tratamiento farmacológico escalonado de acuerdo con el control de la enfermedad. Los antihistamínicos de segunda generación no sedativos son la primera línea de tratamiento. La asociación con descongestivos orales no se recomienda en menores de cuatro años. Los corticoides nasales inhalados son de primera elección en formas moderadas y graves. El presente documento alerta a los pediatras sobre la importancia del diagnóstico precoz, el uso racional del tratamiento farmacológico escalonado y la inmunoterapia específica en niños.

Dermatophagoides spp. hypoallergens design: what has been achieved so far?

Introduction: Allergic illnesses are one of the most prevalent immunological disorders worldwide and house dust mites are important triggers of these diseases. Allergen-specific immunotherapy (AIT) is an alternative treatment to pharmacotherapy and among its technologies, recombinant hypoallergenic derivatives have shown promising features, turn them into safer and more efficient allergy vaccines.Areas covered: Patents and scientific publications referring to advances in the design of Dermatophagoides spp. hypoallergenic molecules. Data were obtained from the Espacenet® and PubMed websites, using different key terms, advanced tools and Boolean operators for searches. The retrieved data were then descriptively analyzed, taking into consideration clinical targets, geographical, temporal, collaborative, and different classification aspects of the productions.Expert opinion: Joint advances of molecular biology, genetic engineering, and bioinformatics technologies led to progresses in the design of Dermatophagoides spp. hypoallergenic derivatives. Collaborative networks seem to be an interesting way not only to improve technologies in AIT but also to boost the number of patents, publications, and grants for researchers. The observed trend for the use of hypoallergenic hybrid molecules was a fundamental AIT advance and this type of molecule appears to be a more attractive product for companies and more convenient, efficient, and safer allergy immunotherapy for patients.

Advances in patent applications related to allergen immunotherapy.

INTRODUCTION: Allergies are among the most prevalent chronic diseases worldwide. Allergen-specific immunotherapy is used as an alternative treatment to pharmacotherapy. These immunotherapies are performed with crude extracts, which have disadvantages when compared to the new approaches, among them are recombinant proteins and hypoallergens. This review aims to assess immunotherapy for allergies through patent application analysis spanning recent decades. AREAS COVERED: Patents referring to allergen immunotherapies used in allergy treatment. Data were obtained from the Espacenet® website, using the Cooperative Patent Classification (CPC) system. Two-hundred-and-one patent applications were analyzed, taking into consideration their classification by the type of technology and applicant. EXPERT OPINION: Allergen-specific immunotherapy represents the only potentially curative therapeutic intervention for the treatment of allergic diseases. The extract-based immunotherapy is being replaced by the use of recombinant allergens, highlighting the hypoallergenic forms, which have low IgE-binding while retaining T-cell reactivity. It is expected that the development of hypoallergens will expand the scope of allergen-specific immunotherapy, especially if associated with alternative systems for expression and delivery systems with future potential. Furthermore, these new developments will likely address the problem of long-term protocols in allergen-specific immunotherapy, thus allowing better patient adherence and compliance.

Alérgenos recombinantes: papel no diagnóstico e na imunoterapia alérgeno-específica / Recombinant allergens: role in diagnosis and in allergen-specific immunotherapy

Nos últimos 30 anos tem havido um avanço notável na identificação, purificação e expressão recombinante de alérgenos relevantes das mais variadas fontes, incluindo ácaros, insetos, mamíferos, polens, alimentos, fungos, látex e outras fontes. Estes avanços resultaram na utilização crescente de alérgenos purificados, naturais ou recombinantes, para melhorar o diagnóstico de alergia pelos métodos que dispomos, incluindo os testes cutâneos de hipersensibilidade imediata, e os métodos in vitro para medida de anticorpos IgE específicos, como ImmunoCAP, ImmunoCAP-ISAC, ELISA e MARIA. Mais recentemente, o uso de alérgenos recombinantes de pólen de bétula (rBet v 1) e de gramas (coquetel de 5 alérgenos) em imunoterapia foi relatado como seguro e eficaz, com resultados comparáveis aos obtidos usando extratos naturais, em pacientes com rinoconjuntivite alérgicos a polens. No presente artigo, apresentamos revisão atualizada do uso de alérgenos recombinantes em diagnóstico de alergia e em imunoterapia alérgeno-específica, incluindo novas estratégias de imunoterapia. Focalizamos na avaliação crítica de estudos que investigaram sensibilidade, especificidade, reatividade cruzada e valor prognóstico de métodos diagnósticos com uso de alérgenos recombinantes versus extratos naturais; nas recomendações atuais para o uso destes novos métodos na prática clínica; e na revisão de estudos clínicos com imunoterapia usando alérgenos recombinantes realizados até o momento.

Over the past 30 years, a great deal of progress has been made in the identification, purification,and recombinant expression of relevant allergens from various sources, including mites, insects,mammals, pollens, foods, fungi, latex, and other sources. These new developments have resultedin an increasing use of purified allergens, either natural or recombinant, to improve the diagnosisof allergy via the methods currently available, including skin tests and in vitro tests for measuringspecific IgE antibodies, e.g., ImmunoCAP, ImmunoCAP-ISAC, ELISA, and MARIA. More recently,the use of recombinant allergens from birch pollen (rBet v 1) and from grass pollen (a cocktailof five allergens) in immunotherapy has been reported to be safe and effective, with resultscomparable to those obtained with natural extracts in patients with rhino-conjunctivitis due topollen allergy. In the present article, we present an up-to-date review on the use of recombinantallergens in the diagnosis of allergy and in allergen-specific immunotherapy, including newstrategies for immunotherapy. We focus on the critical analysis of studies that have investigatedsensitivity, specificity, cross-reactivity, and the prognostic value of diagnostic methods that includerecombinant allergens versus natural extracts; on current recommendations for the use of thesenew methods in clinical practice; and on the review of clinical studies using immunotherapy withrecombinant allergens performed to date.

Dermatite atópica canina e ácaros domésticos: revisão / Canine atopic dermatitis and domestic mites: review

Dermatite Atópica Canina (DAC) é doença comum na clínica de pequenos animais e afeta negativamente,em função de seu caráter crônico, a qualidade de vida dos cães afetados e de seus proprietários. Ácaros domiciliares (AD) são considerados como as principais fontes de alérgenos e a comprovação desta associação,caso a caso, se faz necessária para que medidas preventivas e terapêuticas possam ser indicadas. Esta revisãode literatura tem como objetivo fornecer informações atualizadas sobre a imunopatologia da DAC, as principaisespécies de AD envolvidas, os alérgenos já identificados pelos soros de cães atópicos, os métodos de diagnóstico e protocolos de imunoterapia alérgeno-específica (ASIT). (AU)

Canine Atopic Dermatitis (CAD) is a common chronic disease in small animal practice and adversely affects the quality of life of affected dogs and their owners. Domestic mites (DA) are considered as the main sources of allergens and the proof of this association, case-by-case, is necessary for preventive and therapeutic measures may be indicated. This review aims to provide up-to-date information about the immunopathology of CAD, the main species of DA involves, the allergens have already identified by serafrom atopic dogs, diagnostic methods and protocols of allergen-specific immunotherapy (ASIT). (AU)

Dermatite atópica canina e ácaros domésticos: revisão / Canine atopic dermatitis and domestic mites: review

Dermatite Atópica Canina (DAC) é doença comum na clínica de pequenos animais e afeta negativamente,em função de seu caráter crônico, a qualidade de vida dos cães afetados e de seus proprietários. Ácaros domiciliares (AD) são considerados como as principais fontes de alérgenos e a comprovação desta associação,caso a caso, se faz necessária para que medidas preventivas e terapêuticas possam ser indicadas. Esta revisãode literatura tem como objetivo fornecer informações atualizadas sobre a imunopatologia da DAC, as principaisespécies de AD envolvidas, os alérgenos já identificados pelos soros de cães atópicos, os métodos de diagnóstico e protocolos de imunoterapia alérgeno-específica (ASIT).

Canine Atopic Dermatitis (CAD) is a common chronic disease in small animal practice and adversely affects the quality of life of affected dogs and their owners. Domestic mites (DA) are considered as the main sources of allergens and the proof of this association, case-by-case, is necessary for preventive and therapeutic measures may be indicated. This review aims to provide up-to-date information about the immunopathology of CAD, the main species of DA involves, the allergens have already identified by serafrom atopic dogs, diagnostic methods and protocols of allergen-specific immunotherapy (ASIT).

Ambiente y estilo de vida en la prevención del asma en el niño: [revisión] / Environment and lifestyle in the prevention of asthma in children: [review]

Se ha planteado que el manejo del niño con antecedentes familiares de atopia que no ha presentado asma, debe incluir medidas de Prevención Primaria que lo puedan proteger de desarrollar esta condición. En los estudios realizados a este respecto, se ha evaluado la influencia de factores dietéticos, ambientales e infecciosos que pudieran tener impacto en la historia natural de la enfermedad. En este artículo se evalúa la evidencia disponible acerca de cada intervención, a fin de dar al médico Pediatra y de Atención Primaria herramientas para hacer recomendaciones apropiadas para los padres.

It has been suggested that the management of children at risk for developing asthma should include Primary Prevention measures in order to protect them against the development of this condition. In the published studies to date, the influence of dietary, environmental, and infectious factors involved has been assessed. In this article, we review the available evidence on each intervention, and give some tools to the Pediatrician and Primary Care Physician to make appropriate recommendations for parents.