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1.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445077

RESUMO

Honeybee venom is a source of proteins with allergenic properties which can result in in various symptoms, ranging from local reactions through to systematic life-threatening anaphylaxis, or even death. According to the World Allergy Organization (WAO), honeybee venom allergy is one of the most common causes of anaphylaxis. Among the proteins present in honeybee venom, 12 protein fractions were registered by the World Health Organization's Allergen Nomenclature Sub-Committee (WHO/IUIS) as allergenic. Most of them are highly immunogenic glycoproteins that cross-react with IgE and, as a consequence, may give false positive results in allergy diagnosis. Allergenic fractions are different in terms of molecular weight and biological activity. Eight of these allergenic fractions have also been identified in honey. This explains frequent adverse reactions after consuming honey in people allergic to venom and sheds new light on the causes of allergic symptoms in some individuals after honey consumption. At the same time, it also indicates the possibility of using honey as a natural source of allergen in specific immunotherapy.


Assuntos
Alérgenos/efeitos adversos , Venenos de Abelha/efeitos adversos , Hipersensibilidade/etiologia , Alérgenos/imunologia , Animais , Venenos de Abelha/imunologia , Abelhas/imunologia , Glicoproteínas/efeitos adversos , Glicoproteínas/imunologia , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Proteínas de Insetos/efeitos adversos , Proteínas de Insetos/imunologia
2.
J Immunol ; 207(4): 1150-1164, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34341167

RESUMO

CARD11 is a multidomain scaffold protein required for normal activation of NF-κB, JNK, and mTOR during Ag receptor signaling. Germline CARD11 mutations cause at least three types of primary immunodeficiency including CARD11 deficiency, B cell expansion with NF-κB and T cell anergy (BENTA), and CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS). CADINS is uniquely caused by heterozygous loss-of-function CARD11 alleles that act as dominant negatives. CADINS patients present with frequent respiratory and skin infections, asthma, allergies, and atopic dermatitis. However, precisely how a heterozygous dominant negative CARD11 allele leads to the development of this CADINS-specific cluster of symptoms remains poorly understood. To address this, we generated mice expressing the CARD11 R30W allele originally identified in patients. We find that CARD11R30W/+ mice exhibit impaired signaling downstream of CARD11 that leads to defects in T, B, and NK cell function and immunodeficiency. CARD11R30W/+ mice develop elevated serum IgE levels with 50% penetrance that becomes more pronounced with age, but do not develop spontaneous atopic dermatitis. CARD11R30W/+ mice display reduced regulatory T cell numbers, but not the Th2 expansion observed in other mice with diminished CARD11 activity. Interestingly, the presence of mixed CARD11 oligomers in CARD11R30W/+ mice causes more severe signaling defects in T cells than in B cells, and specifically impacts IFN-γ production by NK cells, but not NK cell cytotoxicity. Our findings help explain the high susceptibility of CADINS patients to infection and suggest that the development of high serum IgE is not sufficient to induce overt atopic symptoms.


Assuntos
Linfócitos B/imunologia , Proteínas Adaptadoras de Sinalização CARD/imunologia , Imunoglobulina E/imunologia , Células Matadoras Naturais/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Alelos , Animais , Heterozigoto , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL
3.
Nutrients ; 13(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34371828

RESUMO

There is increasing evidence that early introduction of allergenic foods may decrease the risk of developing IgE-mediated food allergy. Patterns of food introduction before the 2015 publication of the Learning Early about Peanut Allergy (LEAP) trial are not well-studied, but are important as a baseline for evaluating subsequent changes in infant feeding practices and potentially food allergy. We performed a retrospective longitudinal study using data from a multicenter cohort of infants hospitalized with bronchiolitis between 2011-2014. The primary outcomes were IgE-mediated egg or peanut allergy by age 3 years. Of 770 participants included in the analysis, 635 (82%) introduced egg, and 221 (27%) introduced peanut by age 12 months per parent report. Four participants had likely egg allergy, and eight participants had likely peanut allergy by age 3 years. Regular infant egg consumption was associated with less egg allergy. The association was suggestive for infant peanut consumption with zero peanut allergy cases. Overall, our results suggest that early introduction of peanut was uncommon before 2015. Although limited by the small number of allergy cases, our results suggest that early introduction of egg and peanut are associated with a decreased risk of developing food allergy, and support recent changes in practice guidelines.


Assuntos
Alérgenos/administração & dosagem , Dieta/métodos , Ingestão de Alimentos/imunologia , Hipersensibilidade Alimentar/imunologia , Fenômenos Fisiológicos da Nutrição do Lactente/imunologia , Alérgenos/imunologia , Arachis/imunologia , Pré-Escolar , Dieta/efeitos adversos , Hipersensibilidade a Ovo/epidemiologia , Hipersensibilidade a Ovo/imunologia , Ovos , Feminino , Hipersensibilidade Alimentar/epidemiologia , Humanos , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Hipersensibilidade a Amendoim/epidemiologia , Hipersensibilidade a Amendoim/imunologia , Estudos Retrospectivos
4.
Ann Clin Lab Sci ; 51(4): 540-545, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452893

RESUMO

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae), an extracellular pathogen lacking a cell wall, causes respiratory infection in adults and children and has been implicated in asthma exacerbation; immunoglobulin (Ig) E may be involved in these exacerbations. Specific IgM and IgG immune response to M. pneumoniae has been reported, but less is known about IgE M. pneumoniae antibody (Ab) responses in asthma. Previous studies in our laboratory demonstrated that asthmatic children have increased IgM M. pneumoniae levels, but not IgE. Thus, we sought to investigate whether past M. pneumoniae infection triggers production of M. pneumoniae-specific IgE Abs in adult subjects with/without asthma. METHODS: M. pneumoniae- IgE and -IgM Ab responses were studied in adult asthmatic (N=22) and non-asthmatic (N=22) subjects (ELISA). Data are reported as antibody index. Threshold detection levels: IgE, IgM: 0.2, 0.9, respectively. RESULTS: M. pneumoniae-IgE Ab levels were low and below the threshold of detection in both asthmatic and non-asthmatics (0.002±0.008 vs. 0.02±0.03; P=0.021). However, specific-IgM levels were slightly higher in non-asthmatics compared with asthmatics (0.96±0.37 vs. 0.79±0.31; P=0.054). M. pneumoniae-IgM Ab positivity was similar in both groups (P=1.0). CONCLUSION: IgM M. pneumoniae Abs may play an important role in non-asthma and persist for months after acute infection. IgE M. pneumoniae Abs may play a less important role in both groups.


Assuntos
Anticorpos Antibacterianos/sangue , Asma/imunologia , Imunoglobulina E/imunologia , Imunoglobulina M/sangue , Mycoplasma pneumoniae/imunologia , Pneumonia por Mycoplasma/imunologia , Adulto , Anticorpos Antibacterianos/imunologia , Asma/sangue , Asma/complicações , Asma/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/etiologia , Prognóstico
5.
Nutrients ; 13(8)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34444795

RESUMO

The COVID-19 pandemic is the most challenging global health crisis of our times. Vaccination against COVID-19 plays a key role to control the current pandemic situation. The risk of allergic reactions to new COVID-19 vaccines is low. However, there is a debate on the safety in allergic patients following post marketing findings by different agencies. Our aim is to understand from current experiences whether children with cow's milk or food allergy are at higher risk than a general population for allergic reactions to COVID-19 vaccines. Current data indicate that patients with a history of allergy to cow's milk or other foods, even if severe, should receive COVID-19 vaccine in a setting with availability of treatments for anaphylactic reactions and under medical supervision. Recipients should be discharged after a protracted observation period of 30 min if no reaction developed.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade a Leite/imunologia , Adolescente , Alérgenos/imunologia , Anafilaxia/etiologia , Animais , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Criança , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Leite/efeitos adversos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , SARS-CoV-2 , Vacinação/efeitos adversos
6.
Viruses ; 13(8)2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34452396

RESUMO

Upon invasion by foreign pathogens, specific antibodies can identify specific foreign antigens and disable them. As a result of this ability, antibodies can help with vaccine production and food allergen detection in patients. Many studies have focused on predicting linear B-cell epitopes, but only two prediction tools are currently available to predict the sub-type of an epitope. NIgPred was developed as a prediction tool for IgA, IgE, and IgG. NIgPred integrates various heterologous features with machine-learning approaches. Differently from previous studies, our study considered peptide-characteristic correlation and autocorrelation features. Sixty kinds of classifier were applied to construct the best prediction model. Furthermore, the genetic algorithm and hill-climbing algorithm were used to select the most suitable features for improving the accuracy and reducing the time complexity of the training model. NIgPred was found to be superior to the currently available tools for predicting IgE epitopes and IgG epitopes on independent test sets. Moreover, NIgPred achieved a prediction accuracy of 100% for the IgG epitopes of a coronavirus data set. NIgPred is publicly available at our website.


Assuntos
Epitopos de Linfócito B/imunologia , Imunoglobulina A/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Aprendizado de Máquina , SARS-CoV-2/imunologia , Algoritmos , COVID-19/imunologia , Proteínas do Envelope de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Epitopos de Linfócito B/química , Humanos , Fosfoproteínas/imunologia , Software , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas da Matriz Viral/imunologia
7.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445142

RESUMO

It is difficult to treat allergic diseases including asthma completely because its pathogenesis remains unclear. House dust mite (HDM) is a critical allergen and Toll-like receptor (TLR) 4 is a member of the toll-like receptor family, which plays an important role in allergic diseases. The purpose of this study was to characterize a novel allergen, Der f 38 binding to TLR4, and unveil its role as an inducer of allergy. Der f 38 expression was detected in the body and feces of Dermatophagoides farinae (DF). Electron microscopy revealed that it was located in the granule layer, the epithelium layer, and microvilli of the posterior midgut. The skin prick test showed that 60% of allergic subjects were Der f 38-positive. Der f 38 enhanced surface 203c expression in basophils of Der f 38-positive allergic subjects. By analysis of the model structure of Der p 38, the expected epitope sites are exposed on the exterior side. In animal experiments, Der f 38 triggered an infiltration of inflammatory cells. Intranasal (IN) administration of Der f 38 increased neutrophils in the lung. Intraperitoneal (IP) and IN injections of Der f 38 induced both eosinophils and neutrophils. Increased total IgE level and histopathological features were found in BALB/c mice treated with Der f 38 by IP and IN injections. TLR4 knockout (KO) BALB/c mice exhibited less inflammation and IgE level in the sera compared to wild type (WT) mice. Der f 38 directly binds to TLR4 using biolayer interferometry. Der f 38 suppressed the apoptosis of neutrophils and eosinophils by downregulating proteins in the proapoptotic pathway including caspase 9, caspase 3, and BAX and upregulating proteins in the anti-apoptotic pathway including BCL-2 and MCL-1. These findings might shed light on the pathogenic mechanisms of allergy to HDM.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Dermatophagoides farinae/imunologia , Hipersensibilidade/imunologia , Ligação Proteica/imunologia , Receptor 4 Toll-Like/imunologia , Sequência de Aminoácidos , Animais , Epitopos/imunologia , Feminino , Humanos , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Pyroglyphidae/metabolismo , Testes Cutâneos/métodos
8.
Nutrients ; 13(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34444737

RESUMO

Tree nuts are considered an important food in healthy diets. However, for part of the world's population, they are one of the most common sources of food allergens causing acute allergic reactions that can become life-threatening. They are part of the Big Eight food groups which are responsible for more than 90% of food allergy cases in the United States, and within this group, almond allergies are persistent and normally severe and life-threatening. Almond is generally consumed raw, toasted or as an integral part of other foods. Its dietary consumption is generally associated with a reduced risk of cardiovascular diseases. Several almond proteins have been recognized as allergens. Six of them, namely Pru du 3, Pru du 4, Pru du 5, Pru du 6, Pru du 8 and Pru du 10, have been included in the WHO-IUIS list of allergens. Nevertheless, further studies are needed in relation to the accurate characterization of the already known almond allergens or putative ones and in relation to the IgE-binding properties of these allergens to avoid misidentifications. In this context, this work aims to critically review the almond allergy problematic and, specifically, to perform an extensive overview regarding known and novel putative almond allergens.


Assuntos
Alérgenos , Antígenos de Plantas , Hipersensibilidade a Noz/imunologia , Prunus dulcis/imunologia , Alérgenos/análise , Alérgenos/imunologia , Animais , Antígenos de Plantas/imunologia , Rotulagem de Alimentos , Humanos , Imunoglobulina E/imunologia , Hipersensibilidade a Noz/epidemiologia
9.
Tuberk Toraks ; 69(2): 167-176, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34256507

RESUMO

Introduction: The diagnosis of asthma is still a difficult problem in cystic fibrosis. There is no consensus on how to define "CF asthma". The aim of this study was to determine the role of bronchodilator response and laboratory evidence of allergy in "CF asthma". Materials and Methods: Patients aged ≥6 years with evaluated bronchodilator response and characteristics of atopy were included in the study. Patients diagnosed with Allergic Bronchopulmonary Aspergillosis or pulmonary exacerbation were excluded. Result: A total of 204 CF patients were evaluated, and 40 who met the criteria were included. Asthma had been diagnosed in ten patients. A positive bronchodilator response was present in 47.3% of the patients tested. Aeroallergen sensitization was present in 52.5% of the patients. While the frequency of recurrent/history of wheezing, family history of atopy and elevated total immunoglobulin E were similar (p> 0.05), the frequencies of inhaled medication use and coexistence of asthma were statistically higher in the group with positive allergen sensitization (p<0.05). The frequencies of positive bronchodilator response (77.7% versus 37.9%) and a family history of asthma/atopy (40% versus. 23%) were found to be similar in CF asthma and CF. There were significant increases in total IgE and allergen-specific IgE and an increase in the frequency of aeroallergen sensitization in CF asthma compared to CF (p<0.05). Conclusions: Although not routinely used in the evaluation of patients, allergen specific-IgE and skin prick test for aeroallergen sensitization may be used as an adjunctive test in patients with suspected clinical findings. The recognition of CF asthma may facilitate the development of targeted therapies.


Assuntos
Asma/diagnóstico , Fibrose Cística/complicações , Alérgenos/imunologia , Asma/complicações , Testes de Provocação Brônquica/métodos , Criança , Humanos , Imunoglobulina E/imunologia , Testes Cutâneos/métodos
10.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201934

RESUMO

Mast cells play a crucial role in the pathogenesis of type 1 allergic reactions by binding to IgE and allergen complexes and initiating the degranulation process, releasing pro-inflammatory mediators. Recently, research has focused on finding a stable and effective anti-allergy compound to prevent or treat anaphylaxis. Dihydromyricetin (DHM) is a flavonoid compound with several pharmacological properties, including free radical scavenging, antithrombotic, anticancer, and anti-inflammatory activities. In this study, we investigated the anti-allergic inflammatory effects and the underlying molecular mechanism of DHM in the DNP-IgE-sensitized human mast cell line, KU812. The cytokine levels and mast cell degranulation assays were determined by enzyme-linked immunosorbent assay (ELISA). The possible mechanism of the DHM-mediated anti-allergic signaling pathway was analyzed by western blotting. It was found that treatment with DHM suppressed the levels of inflammatory cytokines TNF-α and IL-6 in DNP-IgE-sensitized KU812 cells. The anti-allergic inflammatory properties of DHM were mediated by inhibition of NF-κB activation. In addition, DHM suppressed the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and mast cell-derived tryptase production. Our study shows that DHM could mitigate mast cell activation in allergic diseases.


Assuntos
Degranulação Celular/imunologia , Flavonóis/imunologia , Imunoglobulina E/imunologia , Mastócitos/imunologia , NF-kappa B/imunologia , Transdução de Sinais/imunologia , Linhagem Celular , Humanos
11.
Nutrients ; 13(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202484

RESUMO

INTRODUCTION: Allergy to nonspecific lipid transfer protein (nsLTP) is the main cause of plant-food allergy in Spain. nsLTPs are widely distributed in the plant kingdom and have high cross-reactivity but extremely variable clinical expression. Little is known about the natural evolution of this allergy, which complicates management. The objective of this study was to assess the development of allergy to new plant foods in nsLTP-sensitized patients 10 years after diagnosis. METHODS: One hundred fifty-one patients showing specific IgE to nsLTP determined by ISAC (Thermofisher) were included. After clinical workup (i.e., anamnesis, skin test, and challenge when needed), these patients were divided into two groups: 113 patients allergic to one or more plant food (74.5%) and 38 patients not allergic to any plant food (25.1%). Ten years later, a telephone interview was conducted to check whether patients had developed additional allergic reactions to plant foods. RESULTS: Ten years after diagnosis, 35 of the 113 (31%) plant-food-allergic patients sensitized to nsLTP reported reactions to new, previously tolerated plant foods, mainly Rosaceae/Prunoideae fruits and nuts followed by vegetables, Rosacea/Pomoideae fruits, legumes, and cereals. Five out of 38 (13.2%) patients previously sensitized to nsLTP but without allergy to any plant food had experienced allergic reactions to some plant food: two to Rosaceae/Prunoideae fruits, two to Rosaceae/Prunoideae fruit and nuts, and one to legumes. CONCLUSION: Patients sensitized to nsLTP developed allergic reactions to other plant foods, mainly Rosaceae-Prunoideae fruits and nuts. This was more frequent among plant-food-allergic patients than among those who had never had plant-food allergy.


Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Proteínas de Transporte/imunologia , Dessensibilização Imunológica/efeitos adversos , Hipersensibilidade Alimentar/imunologia , Proteínas de Plantas/imunologia , Adulto , Reações Cruzadas/imunologia , Feminino , Seguimentos , Frutas/imunologia , Humanos , Imunoglobulina E/imunologia , Masculino , Nozes/imunologia , Rosaceae/imunologia , Testes Cutâneos , Espanha , Verduras/imunologia
12.
Biomed Pharmacother ; 140: 111726, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34111725

RESUMO

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Asma/tratamento farmacológico , Óleos Vegetais/uso terapêutico , Thymus (Planta) , Alérgenos , Animais , Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Asma/imunologia , Asma/patologia , Citocinas/sangue , Citocinas/imunologia , Células Caliciformes/efeitos dos fármacos , Imunoglobulina E/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Ovalbumina , Óleos Vegetais/farmacologia , Coelhos , Espécies Reativas de Oxigênio/imunologia , Células Th2/imunologia
14.
Ann Allergy Asthma Immunol ; 127(3): 301-305, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34102303

RESUMO

OBJECTIVE: To review the literature and discuss a hypothesis as to why most people do not have allergy. This hypothesis is dependent on the following 3 main components: (1) airborne allergens (eg, from pollen or mites) are weak antigens that induce a B-cell response only in immunologically most reactive subjects (ie, with atopy); (2) a roadblock to production of immunoglobulin E (IgE) is the T helper 2/interleukin 4 requirement for class switch to IgE; (3) activated germinal centers prevent the formation of mature IgE-switched B-cells, creating a second roadblock to IgE production. DATA SOURCES: Transgenic reporter mice and a cross-sectional human cohort. STUDY SELECTIONS: From the mouse studies, we selected the data on histology and tissue-derived cell suspensions published by several groups in 2011 to 2014. From the human cohort, we selected our published microarray data on the levels of allergen-specific IgE and IgG in serum. RESULTS: The immune response to airborne atopic allergens entails both IgE and IgG antibodies rather than just an IgG or IgE response. However, as expected for an immune response without mature germinal centers, the specific IgG levels will be very low, typically in the ng/ml range. CONCLUSION: Control of IgE production is not just through the T helper 2/interleukin 4-mediated class switch. Recent studies suggest that mature germinal centers are likely to provide protection against the development of allergy to airborne allergens, as well. This may explain why allergen exposure does not induce allergen-specific IgE in everyone.


Assuntos
Centro Germinativo/imunologia , Hipersensibilidade/imunologia , Animais , Antígenos/imunologia , Linfócitos B/imunologia , Humanos , Imunoglobulina E/imunologia
15.
Food Chem ; 362: 129879, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34118511

RESUMO

Baked matrices, such as muffin, may help to promote tolerance to food allergens by modifying allergen structure, digestibility, and capacity to stimulate the immune responses. However, the impact of the muffin matrix on the bioaccessibility of allergens in the gastrointestinal tract is not well understood. Muffin containing egg and peanut was subjected to in vitro oral-gastro-duodenal digestion. During gastric digestion, the majority of the egg allergen Gal d 2 and the peanut allergens Ara h 1 and 3 were not bioaccessible. Subsequent duodenal digestion increased allergen bioaccessibility with Gal d 2 and the peanut allergen Ara h 2 proving highly resistant to digestion. The IgE reactivity of bioaccessible peanut allergens was retained to a greater extent than that of egg allergens after oral-gastric digestion. The starch and gluten-rich muffin matrix modifies allergen bioaccessiblity in a manner more similar to baked matrices such as bread, than low water activity matrices such as cookies.


Assuntos
Alérgenos/imunologia , Hipersensibilidade a Ovo , Imunoglobulina E/imunologia , Hipersensibilidade a Amendoim , Albuminas 2S de Plantas/imunologia , Antígenos de Plantas/imunologia , Arachis/química , Culinária , Digestão , Hipersensibilidade Alimentar , Humanos , Proteínas de Membrana/imunologia , Proteínas de Plantas/imunologia
16.
Front Immunol ; 12: 585595, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093515

RESUMO

Introduction: Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from Crocus sativus, shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model. Methods: OVA-induced asthma and PSA model were used to evaluate the effect of safranal in vivo. Lung tissues were collected for H&E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-α, and IFN-γ). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-α, and LTC4) and NF-κB and MAPKs signaling pathway were assessed. Results: Safranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC4, IL-6, and TNF-α. Safranal inhibits NF-κB and MAPKs pathway protein phosphorylation and decreases NF-κB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC4 in serum. Conclusions: Safranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-κB pathways.


Assuntos
Alérgenos/imunologia , Asma/etiologia , Cicloexenos/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Ovalbumina/efeitos adversos , Terpenos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Asma/tratamento farmacológico , Asma/metabolismo , Asma/patologia , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Cicloexenos/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Mastócitos/metabolismo , Camundongos , NF-kappa B/metabolismo , Ovalbumina/imunologia , Transdução de Sinais/efeitos dos fármacos , Terpenos/administração & dosagem
17.
Molecules ; 26(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071080

RESUMO

The main purpose of this study was to investigate whether the blockade of the interaction between the receptor activator of nuclear factor-κB (NF-ĸB) ligand (RANKL) and its receptor RANK as well as the blockade of NF-κB inhibitor kinase (IKK) and of NF-κB translocation have the potential to suppress the pathogenesis of allergic asthma by inhibition and/or enhancement of the production by CD4+ and CD8+ T cells of important cytokines promoting (i.e., IL-4 and IL-17) and/or inhibiting (i.e., IL-10 and TGF-ß), respectively, the development of allergic asthma. Studies using ovalbumin(OVA)-immunized mice have demonstrated that all the tested therapeutic strategies prevented the OVA-induced increase in the absolute number of IL-4- and IL-17-producing CD4+ T cells (i.e., Th2 and Th17 cells, respectively) indirectly, i.e., through the inhibition of the clonal expansion of these cells in the mediastinal lymph nodes. Additionally, the blockade of NF-κB translocation and RANKL/RANK interaction, but not IKK, prevented the OVA-induced increase in the percentage of IL-4-, IL-10- and IL-17-producing CD4+ T cells. These latter results strongly suggest that both therapeutic strategies can directly decrease IL-4 and IL-17 production by Th2 and Th17 cells, respectively. This action may constitute an important mechanism underlying the anti-asthmatic effect induced by the blockade of NF-κB translocation and of RANKL/RANK interaction. Thus, in this context, both these therapeutic strategies seem to have an advantage over the blockade of IKK. None of the tested therapeutic strategies increased both the absolute number and frequency of IL-10- and TGF-ß-producing Treg cells, and hence they lacked the potential to inhibit the development of the disease via this mechanism.


Assuntos
Asma/imunologia , Asma/metabolismo , Animais , Asma/fisiopatologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Hipersensibilidade/fisiopatologia , Imunoglobulina E/imunologia , Interleucina-17/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos
18.
J Vis Exp ; (170)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33999025

RESUMO

Mast cell stabilizers are an essential part of allergy medication. Passive systemic anaphylaxis (PSA) is an animal assay widely used for investigating the effect of a pharmacological agent of interest on mast cells in vivo. As the anaphylactic symptoms are primarily attributed to exocytosis of the granules from mast cells, it is conceived that the agent to cause amelioration of the symptoms has a mast cell stabilizing activity. Despite the fact, it is prudent to confirm the activity by directly demonstrating the decline in the functional activity of mast cells following its treatment. In vitro degranulation assays using an immortalized mast cell line or cultured primary mast cells are routinely employed to that end. The results from the in vitro and in vivo assays may not always be akin to each other; however, as treatment conditions (e.g., treatment dose, time, surrounding environments) for the in vitro assays are often distinct from those for the in vivo assay such as PSA. In pursuit of an in vitro (or ex vivo) assay to reflect more closely the effect of a pharmacological agent on mast cells in vivo, we devised the ex vivo mast cell degranulation assay in which crude peritoneal exudate cells (PECs) isolated from the mice, treated with the agent and administered anti-dinitrophenol (DNP) IgE, were incubated directly with DNP on a carrier protein. It turned out that the assay was not only useful in validating the mast cell stabilizing activity of a pharmacological agent indicated by the in vivo assay but also practical and highly reproducible.


Assuntos
Degranulação Celular/imunologia , Exsudatos e Transudatos/metabolismo , Imunoglobulina E/imunologia , Mastócitos/imunologia , Peritônio/metabolismo , Animais , Células Cultivadas , Masculino , Camundongos
19.
J Immunol ; 206(10): 2301-2311, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33952618

RESUMO

Na+/H+ exchanger regulatory factor 1 (NHERF1), a class I PDZ-binding protein, regulates G protein-coupled receptor signaling in some cell types. NHERF1 also functions as a scaffolding protein and activates non-G protein-coupled receptor signaling pathways, thereby contributing to the pathogenesis of various diseases. Although we have previously shown that NHERF1 regulates mast cell functions, there is little information regarding the role of NHERF1 in other immune cells. How NHERF1 regulates the pathogenesis of allergic disease such as asthma also remains unknown. In the current study, we show that NHERF1 promotes allergic airway inflammation in a house dust mite extract (HDME)-induced mouse model of asthma. Specifically, HDME-specific serum IgE levels, airway leukocyte numbers, and goblet cell hyperplasia were reduced in NHERF1+/- mice as compared with NHERF1+/+ mice. Interestingly, the gene expression of inflammatory (IL-17a, IL-25, and IL-33) as well as T helper 2 (Th2) cytokines (IL-4, IL-5, and IL-13) and several chemokines that recruit eosinophils, neutrophils, and lymphocytes were also decreased in the lungs of NHERF1+/- mice exposed to HDME. Consistent with these observations, microRNAs regulating mucus production, inflammation, Th2 effector functions, and IL-13 expression were increased in the lungs of HDME-treated NHERF1+/- mice. Overall, our studies reveal a unique role for NHERF1 in regulating asthma pathogenesis, and further elucidation of the mechanisms through which NHERF1 modulates allergic inflammation will lead to the development of new therapeutic strategies for asthma.


Assuntos
Asma/sangue , Asma/imunologia , Fosfoproteínas/metabolismo , Pyroglyphidae/imunologia , Trocadores de Sódio-Hidrogênio/metabolismo , Adolescente , Adulto , Animais , Asma/genética , Asma/patologia , Estudos de Casos e Controles , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Células Caliciformes/patologia , Humanos , Hiperplasia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/imunologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Fosfoproteínas/genética , Trocadores de Sódio-Hidrogênio/genética , Adulto Jovem
20.
Int Arch Allergy Immunol ; 182(9): 835-843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33946081

RESUMO

INTRODUCTION: The skin prick test (SPT) is a reliable method to confirm sensitization in IgE-mediated allergic diseases; however, it has been reported to be affected by several personal and environmental factors. Our objective was to determine the factors affecting the skin reactivity to histamine and allergens and investigate whether it differs according to age in terms of reading time. METHODS: A total of 500 patients, aged 4 months-18 years, were enrolled in the study. Wheal and flare reaction sizes were documented as the mean of the longest and the midpoint perpendicular diameter in the 5th, 10th, 15th, and 20th min. Skin reactivity was compared between children >24 and ≤24 months of age. RESULTS: We found larger histamine and allergen wheal sizes in children >24 months than the ones ≤24 months of age (p < 0.001 and p = 0.007, respectively). The duration of maximum histamine reactivity was 15 min for children >24 months whereas 10 min for children ≤24 months of age. The number of children losing their histamine reactivity after 15 and 20 min was significantly higher in the smaller age-group. Multiple regression analysis revealed a larger histamine reactivity in children >24 months of age, having obesity, and having allergen sensitization (p = 0.002, p = 0.003, and p = 0.018, respectively). CONCLUSION: It seems more accurate to evaluate SPT after 10 min in children ≤24 months of age. Cutoff values and ideal measurement time according to individual factors such as age, body mass index, or atopy are needed.


Assuntos
Hipersensibilidade Imediata/diagnóstico , Testes Cutâneos , Adolescente , Fatores Etários , Alérgenos/imunologia , Índice de Massa Corporal , Criança , Pré-Escolar , Humanos , Hipersensibilidade Imediata/etiologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Lactente , Tempo de Reação , Pele/imunologia , Pele/patologia , Testes Cutâneos/métodos , Testes Cutâneos/normas
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