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1.
Methods Mol Biol ; 2578: 219-236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152291

RESUMO

Peptide microarrays are a powerful tool to identify linear epitopes of food allergens in a high-throughput manner. The main advantages of the microarray-based immunoassay are as follows: the possibility to assay thousands of targets simultaneously, the requirement of a low volume of serum, the more robust statistical analysis, and the possibility to test simultaneously several immunoglobulin subclasses. Among them, the last one has a special interest in the field of food allergy, because the development of tolerance to food allergens has been associated with a decrease in IgE and an increase in IgG4 levels against linear epitopes. However, the main limitation to the clinical use of microarray is the automated analysis of the data. Recent studies mapping the linear epitopes of food allergens with peptide microarray immunoassays have identified peptide biomarkers that can be used for early diagnosis of food allergies and to predict their severity or the self-development of tolerance. Using this approach, we have worked on epitope mapping of the two most important food allergens in the Spanish population, cow's milk, and chicken eggs. The final aim of these studies is to define subsets of peptides that could be used as biomarkers to improve the diagnosis and prognosis of food allergies. This chapter describes the protocol to produce microarrays using a library of overlapping peptides corresponding to the primary sequences of food allergens and data acquisition and analysis of IgE and IgG4 binding epitopes.


Assuntos
Hipersensibilidade Alimentar , Imunoglobulina G , Alérgenos , Animais , Biomarcadores , Bovinos , Mapeamento de Epitopos/métodos , Epitopos , Feminino , Hipersensibilidade Alimentar/diagnóstico , Imunoensaio/métodos , Imunoglobulina E/metabolismo , Peptídeos
2.
Food Chem ; 398: 133876, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35969990

RESUMO

Terasi is a fermented shrimp paste in Indonesia. We examined the effect of the Terasi manufacturing process on the abundance of the allergen tropomyosin (TM) and its IgG/IgE-binding ability. Terasi was produced from three shrimps, Akiami (Acetes japonicus), Okiami (Euphausia pacifica), and Isazaami (Neomysis awatchensis). Protein degradation and TM IgE-binding activity were examined by immunoblotting using anti-TM rabbit IgG and competitive enzyme-linked immunosorbent assays using shrimp-allergic patients' sera. The processing caused TM degradation, and the IgG-specific response in Akiami meat disappeared at the second fermentation step but remained in both Okiami and Isazaami Terasi. In contrast, TM IgE-binding in all meats decreased gradually during manufacturing and nearly completely disappeared in Akiami Terasi. Conclusively, Terasi production is an effective manufacturing process to reduce the IgE-binding ability of TM, and Terasi can be recognized as a low allergenic seafood when produced under an appropriate manufacturing condition.


Assuntos
Decápodes , Alimentos Fermentados , Hipersensibilidade Alimentar , Penaeidae , Alérgenos/metabolismo , Animais , Crustáceos/metabolismo , Decápodes/metabolismo , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Indonésia , Penaeidae/metabolismo , Coelhos , Alimentos Marinhos , Tropomiosina/metabolismo
3.
Food Chem ; 403: 134314, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36179632

RESUMO

Tropomyosin (TM) is a major shellfish allergen and a minor fish allergen. Different digestion profiles affect potential allergen anaphylaxis of protein. In this study, released peptides of fish-TM, shrimp-TM, and clam-TM by in vitro digestion of simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and gastrointestinal (GI) were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) based proteomics. Results showed that digestion products of shrimp-TM yielded a lot of peptides matched T/B cell epitopes while core regions matched epitopes were distributed along the entire chain. Pepsin or trypsin-based digestion products of shrimp-TM presented many more peptides matched T/B cell epitopes compared with those of fish-TM and clam-TM. Besides, a differentiating peptide of VEKDKALSNAEGEVAAL (72-88) overlapped T/B cell epitopes could be used as a candidate peptide marker to identify tropomyosin allergen. These findings would supply new insight into the different allergenicity of tropomyosin.


Assuntos
Bivalves , Hipersensibilidade Alimentar , Penaeidae , Perciformes , Animais , Tropomiosina/metabolismo , Mapeamento de Epitopos , Epitopos de Linfócito B/metabolismo , Imunoglobulina E/metabolismo , Proteômica , Penaeidae/metabolismo , Alérgenos/metabolismo , Bivalves/genética , Bivalves/metabolismo , Perciformes/metabolismo , Peptídeos/metabolismo , Digestão
4.
Microbiol Res ; 266: 127234, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36279647

RESUMO

BACKGROUND: Differences in the clinical phenotypes and outcomes of fungus-associated asthma remain unclear. We aimed to investigate the presentation of asthmatics with fungal sensitization and/or positive fungal isolates. METHODS: Clinical characteristics, pulmonary function, microbiological data, allergy test reports, emergency department (ED) visits and hospitalizations were retrieved from the Chang Gung Research Database between 2010 and 2018; the largest electronic medical record-based database in Taiwan. Follow-up care was provided to each patient for 3 years. RESULTS: A total of 30,754 asthmatics were enrolled, and 7976 were eligible for analysis after applying the exclusion criteria. Of these patients, 694 had sputum examinations for fungi. The patients were divided into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n = 386); group 2, positive fungal sensitization (n = 58); group 3, positive fungal isolates (n = 217); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n = 33). Asthmatic patients with fungal sensitization (groups 2 and 4) demonstrated significantly higher IgE levels compared with those without (groups 1 and 3). Group 4 patients had a higher frequency of hospitalization. Amongst patients under Global Initiative for Asthma (GINA) step 4-5 therapies, group 4 asthmatics possessed significantly higher incidence of respiratory failure. CONCLUSIONS: The prevalence of fungal sensitization and fungal isolates from sputum were even across asthmatic severities, but the clinical impact of fungi may be more significant among patients with more severe disease.


Assuntos
Asma , Imunoglobulina E , Imunoglobulina E/uso terapêutico , Taiwan/epidemiologia , Asma/epidemiologia , Asma/tratamento farmacológico , Prevalência , Fungos
5.
Ann Pharmacother ; 57(1): 62-70, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35535458

RESUMO

OBJECTIVE: To review the pharmacology, efficacy, and safety of subcutaneous tezepelumab in the treatment of severe uncontrolled asthma. DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: tezepelumab, Tezspire, AMG157, and MEDI9929. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 2000 and March 2022 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In a phase 2 trial, tezepelumab at low, medium, and high doses reduced the annualized asthma exacerbation rate by 62%, 71%, and 66%, respectively, when compared with placebo (P < 0.001). In addition to significant reduction of asthma exacerbation rate in the overall treatment population, a phase 3 trial showed significant reduction of asthma exacerbation across all subgroups analyzed regardless of serum eosinophil count (EOS), fractionated exhaled nitric oxide (FeNO) level, or allergic status as determined by IgE sensitivity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tezepelumab is indicated to treat nonallergic and noneosinophilic severe uncontrolled asthma phenotypes in addition to type 2 inflammatory asthma. When selecting the most appropriate biologic agent, consider the risks, benefits, and costs. There is a paucity of data on the efficacy of tezepelumab in patients with comorbid conditions. In the case of a patient presenting with uncontrolled severe asthma with such comorbid conditions, it may be prudent to consider a biologic therapy that can target both. CONCLUSION: Tezepelumab has shown clinical utility in severe uncontrolled asthma regardless of phenotype, fulfilling the need for treatment options in individuals with severe, uncontrolled, noneosinophilic, and nonallergic asthma.


Assuntos
Antiasmáticos , Asma , Humanos , Óxido Nítrico/uso terapêutico , Asma/tratamento farmacológico , Imunoglobulina E/uso terapêutico , Fatores Biológicos/uso terapêutico , Antiasmáticos/efeitos adversos , Método Duplo-Cego
6.
Allergol. immunopatol ; 50(6): 22-31, 01 nov. 2022. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-211505

RESUMO

Chronic inflammation in the airway passage leads to the clinical syndrome of pediatric asthma. Allergic reactions caused by bacterial, viral, and fungal infection lead to the immune dis-balance which primes T helper cells (Th2), a specific cluster of differentiation 4 (CD4) T cell differentiation. This favors the Th2-specific response by activating the inter-leukin 4/interleukin 13 (IL-4/IL-13) cytokine signaling and further activates the secretion of immunoglobulin E (IgE). IL-13 develops bronchial asthma by elevating bronchial hyperresponsiveness and enables production of immunoglobulin M (IgM) and IgE. The present study aims to target IL-13 signaling using molecular docking and understanding molecular dynamic simulation (MDS) to propose a compelling candidate to treat asthma. We developed a library of available allergic drugs (n=20) and checked the binding affinity against IL-13 protein (3BPN.pdb) through molecular docking and confirmed the best pose binding energy of –3.84 and –3.71 for epinephrine and guaifenesin, respectively. Studying the interaction of hydrogen bonds and Van der Walls, it is estimated that electrostatic energy is sufficient to interact with the active site of the IL-13 and has shown to inhibit inflammatory signaling. These computational results confirm epinephrine and guaifenesin as potential ligands showing potential inhibitory activity for IL-13 signaling. This study also suggests the designing of a new ligand and screening of a large cohort of drugs, in the future, to predict the exact mechanism to control the critical feature of asthma (AU)


Assuntos
Animais , Camundongos , Asma , Epinefrina/uso terapêutico , Receptores Adrenérgicos/uso terapêutico , Guaifenesina/uso terapêutico , Hipersensibilidade Imediata , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina E , Interleucina-13/metabolismo , Camundongos Endogâmicos BALB C
7.
Allergy Asthma Proc ; 43(6): 519-528, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36335414

RESUMO

Background: There are no well-defined data that help predict the recurrence risk of urticaria after omalizumab cessation in elderly patients with chronic spontaneous urticaria (CSU). Objective: We aimed to evaluate the effectiveness and safety of omalizumab and to determine the possible predictive factors for recurrence after omalizumab cessation in the elderly with CSU. Methods: A total of 193 patients with CSU treated with omalizumab were included and divided into two groups according to age: group 1, ages 18-64 years (n = 127), and group 2, ages ≥ 65 years (n = 66). Demographics, clinical features, immunoglobulin G (IgG) anti-thyroid peroxidase antibody (anti-TPO), serum total IgE were analyzed. The IgG anti-TPO/total IgE ratio was calculated. Pretreatment 7-day urticaria activity scores, medication scores, and urticaria control test results were compared with those after treatment periods. Adverse effects were also evaluated. Results: The most common adverse effect of omalizumab treatment was injection-site reactions (4.7%) in both groups. Omalizumab was ceased after 24 weeks in 40.9% and in 73.1% in group 1 and group 2, respectively (p < 0.001). CSU recurred after omalizumab discontinuation in 9 and 15 patients in group 1 and in group 2, respectively (p < 0.001). The median baseline IgG anti-TPO was higher in patients with recurrent CSU in group 2 than in those in group 1 (p = 0.002). In group 2, the cutoff values of IgG anti-TPO and the IgG anti-TPO/total IgE ratio were 54.83 IU/mL and 0.45 for recurrence, respectively. Conclusion: Omalizumab is effective and safe in elderly patients with CSU. The serum baseline IgG anti-TPO level and the IgG anti-TPO/total IgE ratio could serve as predictors of recurrence in CSU after omalizumab cessation in elderly patients.


Assuntos
Antialérgicos , Urticária Crônica , Urticária , Humanos , Idoso , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Omalizumab/efeitos adversos , Doença Crônica , Urticária/tratamento farmacológico , Imunoglobulina G , Imunoglobulina E , Antialérgicos/efeitos adversos , Resultado do Tratamento
8.
Allergy Asthma Proc ; 43(6): 533-542, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36335421

RESUMO

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.


Assuntos
Anafilaxia , Hipersensibilidade a Noz , Hipersensibilidade a Amendoim , Humanos , Nozes/efeitos adversos , Arachis , Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Anafilaxia/etiologia , Estudos Retrospectivos , Hipersensibilidade a Noz/diagnóstico , Hipersensibilidade a Noz/epidemiologia , Hipersensibilidade a Amendoim/diagnóstico , Hipersensibilidade a Amendoim/epidemiologia , Imunoglobulina E , Alérgenos
9.
Allergol Immunopathol (Madr) ; 50(6): 22-31, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36335442

RESUMO

Chronic inflammation in the airway passage leads to the clinical syndrome of pediatric asthma. Allergic reactions caused by bacterial, viral, and fungal infection lead to the immune dis-balance which primes T helper cells (Th2), a specific cluster of differentiation 4 (CD4) T cell differentiation. This favors the Th2-specific response by activating the inter-leukin 4/interleukin 13 (IL-4/IL-13) cytokine signaling and further activates the secretion of immunoglobulin E (IgE). IL-13 develops bronchial asthma by elevating bronchial hyperresponsiveness and enables production of immunoglobulin M (IgM) and IgE. The present study aims to target IL-13 signaling using molecular docking and understanding molecular dynamic simulation (MDS) to propose a compelling candidate to treat asthma. We developed a library of available allergic drugs (n=20) and checked the binding affinity against IL-13 protein (3BPN.pdb) through molecular docking and confirmed the best pose binding energy of -3.84 and -3.71 for epinephrine and guaifenesin, respectively. Studying the interaction of hydrogen bonds and Van der Walls, it is estimated that electrostatic energy is sufficient to interact with the active site of the IL-13 and has shown to inhibit inflammatory signaling. These computational results confirm epinephrine and guaifenesin as potential ligands showing potential inhibitory activity for IL-13 signaling. This study also suggests the designing of a new ligand and screening of a large cohort of drugs, in the future, to predict the exact mechanism to control the critical feature of asthma.


Assuntos
Asma , Guaifenesina , Hipersensibilidade , Humanos , Criança , Animais , Camundongos , Interleucina-13/metabolismo , Células Th2 , Simulação de Acoplamento Molecular , Guaifenesina/metabolismo , Guaifenesina/uso terapêutico , Imunoglobulina E , Epinefrina/uso terapêutico , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina , Modelos Animais de Doenças
10.
Allergol Immunopathol (Madr) ; 50(6): 71-75, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36335448

RESUMO

Allergic rhinitis and asthma are the main airway diseases with a higher prevalence. Eosinophilic inflammation, airway hyperresponsiveness, mucus hypersecretion, and reversible airflow obstruction are immunopathogenesis symptoms of rhinitis and asthma. Crotonic acid has bio-activity on the inflammation, and gluconic acid as chelator may protect crotonic acid activity in airway and together may control allergic rhinitis and asthma.Allergic rhinitis and asthma mice models were treated with crotonic and gluconic acids. The total IgE, histamine, IL-4, IL-5, and IL-13 levels were measured. In lung tissues, goblet cell hyperplasia, mucus hypersecretion, and inflammation were evaluated.The level of IL-5, goblet cell hyperplasia, and perivascular and peribronchial inflammation were controlled by crotonic acid in asthma and allergic rhinitis groups. But, total IgE, hista-mine, IL-4, and IL-13 levels, and mucus hypersecretion had no significant changes between treated and nontreated asthma and rhinitis groups.


Assuntos
Asma , Rinite Alérgica , Rinite , Camundongos , Animais , Interleucina-13 , Interleucina-4 , Crotonatos/uso terapêutico , Amidas/uso terapêutico , Hiperplasia , Interleucina-5 , Asma/tratamento farmacológico , Asma/patologia , Rinite Alérgica/tratamento farmacológico , Imunoglobulina E , Inflamação , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Citocinas , Líquido da Lavagem Broncoalveolar
11.
Vet Dermatol ; 33(6): 527-533, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36336575

RESUMO

Background - There is lack of studies evaluating the repeatability and reproducibility of the interpretation of intradermal testing in dogs with atopic dermatitis (AD). Objectives - To evaluate the repeatability and reproducibility of the interpretation of intradermal test results in dogs with AD. For comparison, the repeatability of allergen-specific immunoglobulin (Ig)E serology also was examined. Materials and methods - Twenty dogs with AD were used. Intradermal test included injections of known negative and positive controls, and of 25 masked injections of 10 allergens/controls, that were selected randomly and injected at random positions. Reactions to the 25 masked allergens/controls were scored (positive/negative) subjectively by three independent examiners followed by an objective assessment. Allergen-specific IgE serology was performed in blinded duplicate samples collected from all dogs for nine of 10 of the same allergens. Results - Kappa values of intraobserver repeatability (≥2 injections of the same allergen to different positions of the same dog) varied between -0.53 and 0.8 (subjective evaluations), and between 0.03 and 1 (objective evaluation). When the repeatability of the serological test was examined k = 0.91. Kappa values for the interobserver reproducibility (objective and three subjective evaluations of the same allergen injected at the same position of the same dog) varied between 0.6 and 0.74 (overall 0.67). Conclusions and clinical relevance - Intraobserver repeatability of the subjective and objective evaluation of IDT results varied from good to poor and depended on the number of times the same allergen was injected, whereas interobserver reproducibility varied from substantial to moderate. Further studies are needed to optimise the repeatability and reproducibility of IDT in dogs.


Contexte - Il existe un manque d'études évaluant la répétabilité et la reproductibilité de l'interprétation des tests intradermiques chez les chiens atteints de dermatite atopique (DA). Objectifs - Évaluer la répétabilité et la reproductibilité de l'interprétation des résultats des tests intradermiques chez les chiens atteints de MA. À des fins de comparaison, la répétabilité de la sérologie de l'immunoglobuline (Ig)E spécifique de l'allergène a également été examinée. Matériels et méthodes - Vingt chiens atteints de MA ont été utilisés. Le test intradermique comprenait des injections de contrôles négatifs et positifs connus, et de 25 injections masquées de 10 allergènes/contrôles, qui ont été sélectionnés au hasard et injectés à des positions aléatoires. Les réactions aux 25 allergènes/contrôles masqués ont été notées (positives/négatives) subjectivement par trois examinateurs indépendants, suivies d'une évaluation objective. La sérologie IgE spécifique de l'allergène a été réalisée dans des échantillons en double en aveugle prélevés sur tous les chiens pour neuf des 10 allergènes identiques. Résultats - Les valeurs kappa de répétabilité intra-observateur (≥2 injections du même allergène à différentes positions du même chien) variaient entre -0,53 et 0,8 (évaluations subjectives), et entre 0,03 et 1 (évaluation objective). Lorsque la répétabilité du test sérologique a été examinée, k = 0,91. Les valeurs de Kappa pour la reproductibilité interobservateur (évaluations objective et trois évaluations subjectives du même allergène injecté au même endroit du même chien) variaient entre 0,6 et 0,74 (globalement 0,67). Conclusions et pertinence clinique - La répétabilité intra-observateur de l'évaluation subjective et objective des résultats IDT variait de bonne à mauvaise et dépendait du nombre d'injections d'un même allergène, alors que la reproductibilité inter-observateur variait de substantielle à modérée. D'autres études sont nécessaires pour optimiser la répétabilité et la reproductibilité de l'IDT chez le chien.


Introducción- faltan estudios que evalúen la repetibilidad y la reproducibilidad de la interpretación de las pruebas intradérmicas en perros con dermatitis atópica (AD). Objetivos- evaluar la repetibilidad y reproducibilidad de la interpretación de los resultados de las pruebas intradérmicas en perros con AD. A modo de comparación, también se examinó la repetibilidad de la serología de inmunoglobulina (Ig)E específica de alérgeno. Materiales y métodos - Se utilizaron 20 perros con AD. La prueba intradérmica incluyó inyecciones de controles positivos y negativos conocidos, y de 25 inyecciones enmascaradas de 10 alérgenos/controles, que se seleccionaron al azar y se inyectaron en posiciones aleatorias. Las reacciones a los 25 alérgenos/controles enmascarados fueron calificadas (positivas/negativas) subjetivamente por tres examinadores independientes seguido de una evaluación objetiva. La serología de IgE específica para alérgenos se realizó en muestras duplicadas ciegas recolectadas de todos los perros para nueve de 10 de los mismos alérgenos. Resultados - Los valores Kappa de repetibilidad intraobservador (≥2 inyecciones del mismo alérgeno en diferentes posiciones del mismo perro) variaron entre -0,53 y 0,8 (evaluaciones subjetivas) y entre 0,03 y 1 (evaluación objetiva). Cuando se examinó la repetibilidad de la prueba serológica k = 0,91. Los valores de Kappa para la reproducibilidad interobservador (objetivo y tres evaluaciones subjetivas del mismo alérgeno inyectado en la misma posición del mismo perro) variaron entre 0,6 y 0,74 (en general, 0,67). Conclusiones y relevancia clínica- la repetibilidad intraobservador de la evaluación subjetiva y objetiva de los resultados de la IDT varió de buena a mala y dependió del número de veces que se inyectó el mismo alérgeno, mientras que la reproducibilidad interobservador varió de sustancial a moderada. Se necesitan más estudios para optimizar la repetibilidad y reproducibilidad de IDT en perros.


Contexto - Há poucos estudos avaliando a repetibilidade e reprodutibilidade da interpretação do teste intradérmico em cães com dermatite atópica (DA). Objetivos - Avaliar a repetibilidade e reprodutibilidade da interpretação dos resultados de testes intradérmicos em cães com DA. Para comparação, a repetibilidade da sorologia com imunoglobulinas (Ig)E alérgeno-específicas foi também avaliada. Materiais e métodos - Foram utilizados 20 cães com DA. O teste intradérmico incluiu injeções de controles negativos e positivos conhecidos e de 25 injeções mascaradas de 10 alérgenos/controles, que foram selecionados aleatoriamente e injetadas em posições aleatórias. As reações aos 25 alérgenos/controles mascarados foram pontuadas (positiva/negativa) subjetivamente por três examinadores independentes, seguidas de uma avaliação objetiva. A sorologia de IgE específica para alérgenos foi realizada em amostras duplicadas cegas coletadas de todos os cães para nove de 10 dos mesmos alérgenos. Resultados - Os valores Kappa de repetibilidade intraobservador (≥2 injeções do mesmo alérgeno em diferentes posições do mesmo cão) variaram entre -0,53 e 0,8 (avaliação subjetiva) e entre 0,03 e 1 (avaliação objetiva). Quando examinada a repetibilidade do teste sorológico k=0,91. Os valores de Kappa para a reprodutibilidade interobservador (objetiva e três avaliações subjetivas do mesmo alérgeno injetado na mesma posição do mesmo cão) variaram entre 0,6 e 0,74 (total 0,67). Conclusões e relevância clínica - A repetibilidade intraobservador da avaliação subjetiva e objetiva dos resultados do IDT variou de boa a ruim e dependeu do número de vezes que o mesmo alérgeno foi injetado, enquanto a reprodutibilidade interobservador variou de substancial a moderada. Mais estudos são necessários para otimizar a repetibilidade e reprodutibilidade do IDT em cães.


Assuntos
Dermatite Atópica , Doenças do Cão , Cães , Animais , Dermatite Atópica/diagnóstico , Dermatite Atópica/veterinária , Reprodutibilidade dos Testes , Testes Intradérmicos/veterinária , Testes Intradérmicos/métodos , Imunoglobulina E , Alérgenos
12.
Front Immunol ; 13: 1020064, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389746

RESUMO

Due to the wide scope and persistence of COVID-19´s pandemic, post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. SARS-CoV-2, in line with other infectious agents, has the capacity to activate dormant human endogenous retroviral sequences ancestrally integrated in human genomes (HERVs). This activation was shown to relate to aggravated COVID-19 patient´s symptom severity. Despite our limited understanding of how HERVs are turned off upon infection clearance, or how HERVs mediate long-term effects when their transcription remains aberrantly on, the participation of these elements in neurologic disease, such as multiple sclerosis, is already settling the basis for effective therapeutic solutions. These observations support an urgent need to identify the mechanisms that lead to HERV expression with SARS-CoV-2 infection, on the one hand, and to answer whether persistent HERV expression exists in post-COVID-19 condition, on the other. The present study shows, for the first time, that the HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Moreover, increased anti-SARS-CoV-2 immunoglobulins in post-COVID-19 condition, particularly high anti-SARS-CoV-2 immunoglobulin levels of the E isotype (IgE), seem to strongly correlate with deteriorated patient physical function (r=-0.8057, p<0.01). These results indicate that HERV-W ENV antigenemia and anti-SARS-CoV-2 IgE serology should be further studied to better characterize post-COVID-19 condition pathogenic drivers potentially differing in subsets of patients with various symptoms. They also point out that such biomarkers may serve to design therapeutic options for precision medicine in post-COVID-19 condition.


Assuntos
COVID-19 , Retrovirus Endógenos , Esclerose Múltipla , Humanos , SARS-CoV-2 , Imunoglobulina E
13.
Front Immunol ; 13: 1032909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389804

RESUMO

IgG4 is a subclass of IgG antibody with a unique molecular feature of (Fragment antigen- binding) Fab-arm exchange, allowing bispecific antigen binding in a mono-valent manner. With low binding affinity to C1q and Fcγreceptors, IgG4 is incapable of forming immune complexes and activating the complement pathway, exhibiting a non-inflammatory feature. IgG4 is produced similarly to IgE and is considered a modified reaction to IgE class-switching response under certain conditions. It could also counteract IgE-activated inflammation. However, the clinical significance of IgG4 in allergic diseases is complex and controversial. Three viewpoints have been suggested to describe the role of IgG4. IgG4 can act as a tolerance-inducer to play a protective role under repeated and rapid incremental dosing of allergen exposure in allergen immunotherapy (AIT), supported by allergies in cat raisers and venom desensitization in beekeepers. Another viewpoint accepted by mainstream specialists and guidelines of Food Allergy and Management in different countries points out that food-specific IgG4 is a bystander in food allergy and should not be used as a diagnostic tool in clinical work. However, eosinophilic esophagitis (EoE) investigation revealed a direct clinical relevance between physiopathology and serum IgG4 in cow milk and wheat. These factors indicate that allergen-specific IgG4 plays a multifaceted role in allergic diseases that is protective or pathogenic depending on different allergens or exposure conditions.


Assuntos
Alérgenos , Hipersensibilidade Alimentar , Animais , Feminino , Bovinos , Imunoglobulina G , Imunoglobulina E , Hipersensibilidade Alimentar/terapia , Testes Imunológicos
14.
Front Public Health ; 10: 1038141, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407984

RESUMO

Design: There is a strong correlation between dietary intake and allergic diseases. Ultra-processed foods (UPFs) are gradually becoming dominant worldwide and causing health problems for children and adults. We hope to determine whether links exist between UPFs and allergic symptoms. Methods: We investigated data from 2,736 children (16-19 years) and 4,256 adults (≥20 years) from the National Health and Nutritional Examination Survey (NHANES) 2005-2006. The associations between the mean UPFs contribution to total energy intake and all allergic symptoms (IgE, current asthma, allergy, rash, sneeze, wheeze, eczema, and hay fever) were estimated by weighted multivariate logistic regression. Results: Logistic regression analysis showed UFPs were negatively associated with IgE levels in children. Those with higher quartiles had a reduced risk from 16% (OR, 0.84, 95%CI, 0.55 to 1.28) to 34% (OR, 0.66, 95%CI, 0.49 to 0.89), p for trend = 0.006. UPFs were also positively related to current asthma in children with an increased risk of 11% (OR, 1.11, 95%CI, 0.79 to 1.56) to 76% (OR, 1.76, 95%CI, 1.10 to 2.82), p for trend = 0.0393. UPFs were also associated with eczema in girls. But there was no association observed between UPFs and allergic symptoms in adults. Conclusion: Our results suggested that UPFs assessed by the NOVA system were associated with IgE, current asthma in children, and eczema in girls. These results further support the need to test the association of modern dietary patterns with allergic symptoms.


Assuntos
Asma , Eczema , Rinite Alérgica Sazonal , Humanos , Criança , Adulto , Feminino , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Eczema/epidemiologia , Eczema/etiologia , Rinite Alérgica Sazonal/complicações , Asma/epidemiologia , Asma/complicações , Imunoglobulina E
15.
Medicine (Baltimore) ; 101(45): e31031, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397403

RESUMO

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but "social support." Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.


Assuntos
Asma Induzida por Aspirina , Eosinofilia , Pólipos Nasais , Rinite , Sinusite , Humanos , Estudos Retrospectivos , Rinite/complicações , Rinite/tratamento farmacológico , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Sinusite/patologia , Doença Crônica , Imunoglobulina E
16.
Nat Commun ; 13(1): 6646, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333296

RESUMO

While food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs. with allergic reactions upon food challenge after a withdrawal period; n = 21 vs. 30 respectively among total 120 intent-to-treat participants). Lower frequencies of naïve CD8+ T cells and terminally differentiated CD57+CD8+ T cell subsets at baseline (pre-OIT) are associated with SU. Frequency of naïve CD8+ T cells shows a significant positive correlation with peanut-specific and Ara h 2-specific IgE levels at baseline. Higher frequencies of IL-4+ and IFNγ+ CD4+ T cells post-OIT are negatively correlated with SU. Our findings provide evidence that an immune signature consisting of certain CD8+ T cell subset frequencies is potentially predictive of SU following OIT.


Assuntos
Hipersensibilidade a Amendoim , Hipersensibilidade a Amendoim/terapia , Dessensibilização Imunológica/métodos , Imunoglobulina E , Linfócitos T CD8-Positivos , Estudos de Viabilidade , Administração Oral , Arachis , Alérgenos , Fatores Imunológicos , Diferenciação Celular
17.
Sci Rep ; 12(1): 18910, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344553

RESUMO

Overproduction of mucins in the airways donates largely to airway blockage in asthma patients. Glycoprotein MUC7 plays a role in the clearance of bacteria and has anti-candidacidal criteria. Our goal was to investigate the association between the MUC7 variable number of tandem repeats (VNTR) polymorphism and bronchial asthma among Egyptian children. The MUC7 VNTR polymorphism was investigated among 100 children with bronchial asthma and 100 healthy controls using polymerase chain reaction (PCR) method. Serum levels of immunoglobulin E (IgE), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta1 (TGF-ß1) were assessed by enzyme-linked immunosorbent assay (ELISA) technique. The frequencies of 6*5 genotype, 5*5 genotype, (6*5 + 5*5) genotypes, and MUC7*5 allele of the MUC7 VNTR variant were significantly lower among asthmatic patients than controls (p < 0.015, OR = 0.39, 95% CI = 0.19-0.81; p = 0.03, OR = 0.18, 95% CI = 0.04-0.86; p < 0.001, OR = 0.29, 95% CI = 0.15-0.58; p < 0.001, OR = 0.3, 95% CI = 0.17-0.55, respectively). The (6*5 + 5*5) genotypes of the MUC7 VNTR variant were not associated with the clinical manifestations and serum levels of IgE, TNF-α, and TGF-ß1 among asthmatic patients (p ˃ 0.05). In conclusion, the (6*5 + 5*5) genotypes of the MUC7 VNTR variant may have a protective role for bronchial asthma in Egyptian children.


Assuntos
Asma , Polimorfismo Genético , Criança , Humanos , Fator de Crescimento Transformador beta1/genética , Repetições Minissatélites , Fator de Necrose Tumoral alfa/genética , Egito , Asma/genética , Genótipo , Imunoglobulina E/genética , Predisposição Genética para Doença , Mucinas/genética , Proteínas e Peptídeos Salivares/genética
18.
Int J Mol Sci ; 23(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362241

RESUMO

Efficient characterization of IgE antibodies and their glycan structures is required for understanding their function in allergy and in the emerging AllergoOncology field for antibody immunotherapy. We report the generation, glyco-profiling and functional analysis of native and sialic acid-deficient glyco-engineered human IgE. The antibodies produced from human embryonic kidney cells were purified via a human IgE class-specific affinity matrix and structural integrity was confirmed by SDS-PAGE and size-exclusion chromatography (SEC). Purified IgEs specific for the tumor-associated antigens Chondroitin Sulfate Proteoglycan 4 (CSPG4-IgE) and Human Epidermal Growth Factor Receptor 2 (HER2-IgE) were devoid of by-products such as free light chains. Using neuraminidase-A, we generated sialic acid-deficient CSPG4-IgE as example glyco-engineered antibody. Comparative glycan analyses of native and glyco-engineered IgEs by Hydrophilic interaction liquid chromatography (HILIC)-high performance liquid chromatography (HPLC) indicated loss of sialic acid terminal residues and differential glycan profiles. Native and glyco-engineered CSPG4-IgEs recognized Fc receptors on the surface of human FcεRI-expressing rat basophilic leukemia RBL-SX38 cells, and of CD23/FcεRII-expressing human RPMI-8866 B-lymphocytes and bound to CSPG4-expressing A2058 human melanoma cells, confirming Fab-mediated recognition. When cross-linked on the cell surface, both IgEs triggered RBL-SX38 degranulation. We demonstrate efficient generation and functional competence of recombinant native and sialic acid-deficient IgEs.


Assuntos
Imunoglobulina E , Ácido N-Acetilneuramínico , Ratos , Animais , Humanos , Receptores de IgE/metabolismo , Receptores Fc , Cromatografia em Gel , Antígenos de Neoplasias
19.
J Tradit Chin Med ; 42(6): 858-868, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36378042

RESUMO

OBJECTIVE: To use evidence-based medicine to explore the efficacy of acupoint application (AA) for allergic rhinitis (AR) at different time points and its safety. METHODS: We searched 7 databases (PubMed, Cochrane, Embase, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, and China Biology Medicine disc) as well as the international clinical trial registration platform from January 2010 to March 2020 for randomized controlled trials (RCTs) comparing the efficacy of AA versus placebo, Western Medicine or other alternative therapies on AR. Risk of bias was assessed according to the Cochrane handbook, and statistical analysis was performed using RevMan 5.3. Outcomes included the total effective rate, recurrence rate, total nasal symptom score (TNSS), visual analogue scale (VAS), quality of life measured by the Rhinitis Quality of Life Questionnaire (RQLQ) or Short Form-36 (SF-36), adverse events, and biomarkers including immunoglobulin E (IgE), peripheral blood eosinophil count (EOS), interleukin-4 (IL-4), and interferon gamma (INF-γ). RESULTS: Twenty-eight RCTs involving 3282 participants were included. The short-term and long-term efficacy of AA was significantly better than placebo, including better total effective rate [: 3.05, 95% (1.84, 5.07), after treatment; : 9.29, 95% (2.57, 33.66), at 6 months], lower recurrence rate [: 0.55, 95% (0.45, 0.66), at 6 months; : 0.65, 95% (0.57, 0.74), at 1 year], lower TNSS [: -3.09, 95% (-3.58, -2.61), after treatment], and lower RQLQ [: -14.79, 95% (-21.49, -8.10), after treatment; : -11.92, 95% (-17.40, -6.45), at 4-6 months]. Compared with Western Medicine, AA had better long-term total effective rate [: 1.33, 95%CI (1.05, 1.69), at 3 months; : 1.49, 95% 1.22 to 1.81, at 1 year) and lower recurrence rate [: 0.48, 95% (0.39, 0.58), at 6 months; : 0.45, 95% (0.33, 0.60), at 1 year]. AA had better long-term total effective rate versus acupuncture [: 2.06, 95% (1.28, 3.31), at 1 year] or oral Chinese medicine [: 1.21, 95% (1.09, 1.34), ≥ 6 months]. Both AA and Western Medicine can reduce serum levels of IgE, EOS, and IL-4 after treatment. The main adverse event of AA was local skin reaction without systemic side effects. CONCLUSIONS: The short-term (within one month) and long-term (at 3 months, 6 months and 1 year) efficacy of acupoint application on AR was better than that of placebo. The long-term efficacy of acupoint application was superior to that of Western Medicine (at 3 months, 6 months and 1 year), oral Chinese medicine (at more than 6 months) and acupuncture (at 1 year). AA can reduce serum IgE, EOS, and IL-4 level of AR patients in a short run. Acupoint application is safe, but severe skin reactions can reduce patient compliance.


Assuntos
Pontos de Acupuntura , Rinite Alérgica , Humanos , Interleucina-4 , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite Alérgica/terapia , Imunoglobulina E
20.
Pediatr Allergy Immunol ; 33(11): e13867, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36433848

RESUMO

BACKGROUND: In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only. TARGET: To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (µl) of serum. METHODS: We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank-order correlation coefficient and Bland-Altmann plots. RESULTS: The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE-Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p < .001), (rho 0.87, p < .001), (rho 0.84, p < .001), respectively. The novel molecular SX01 test detected IgE-Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules. DISCUSSION: Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1.


Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade Respiratória , Humanos , Cães , Animais , Alérgenos , Imunoglobulina E , Dermatophagoides pteronyssinus
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