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1.
Mol Immunol ; 116: 140-150, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31654938

RESUMO

BACKGROUND: Non-specific lipid transfer proteins (LTPs) are important allergens in fruits, pollen, vegetables, nuts and latex. Due to their compact structure, LTPs are highly resistant to heat treatment. Here, Art v 3 from mugwort pollen and Pru p 3 from peach were used as model allergens to in-depth investigate structural and immunological properties upon thermal treatment at different buffer conditions. METHODS: Recombinant Art v 3 and Pru p 3 were purified from E. coli and incubated at 95 °C up to 120 min using sodium phosphate buffer pH 3.4 or 7.3. Physicochemical properties of allergens were analyzed in circular dichroism spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, size exclusion chromatography, and mass spectrometry. The crystal structure of Art v 3.0201 was determined to 1.9 Šresolution. IgG and IgE binding was investigated in ELISA using murine and LTP allergic patients' sera. RESULTS: Highly pure and homogenous recombinant allergens were obtained from bacterial production. The crystal structure of Art v 3.0201 revealed an antiparallel four helix bundle with a C-terminal extension mediating an asymmetric, transient dimer interface and differently sized cavities. Both allergens showed high thermal stability at acidic conditions. In contrast, extensive heat treatment in neutral buffer induced irreversible structural changes due to lanthionine-based cysteine rearrangement. This fostered loss of the typical α-helical structure, increased molecular size and abrogation of IgG and IgE binding epitopes. Pru p 3 lost its structural integrity at shorter heat stress duration than Art v 3, which did however only partially affect the molecule's IgE binding epitopes. CONCLUSION: During thermal treatment, susceptibility to structural changes of the LTP-fold is highly dependent on the surrounding environment but also on intrinsic features of individual LTPs. This is a crucial fact to consider when processing LTP-containing food or food products as this will directly influence their allergenic potential.


Assuntos
Alanina/análogos & derivados , Antígenos de Plantas/metabolismo , Proteínas de Transporte/metabolismo , Cisteína/metabolismo , Proteínas de Plantas/metabolismo , Sulfetos/metabolismo , Alanina/metabolismo , Sequência de Aminoácidos , Animais , Artemisia/metabolismo , Reações Cruzadas/fisiologia , Epitopos/metabolismo , Escherichia coli/metabolismo , Hipersensibilidade Alimentar/metabolismo , Humanos , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Camundongos , Pólen/metabolismo , Prunus/metabolismo
2.
Nutrients ; 11(8)2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349704

RESUMO

Epidemiological studies identified raw cow's milk consumption as an important environmental exposure that prevents allergic diseases. In the present study, we investigated whether raw cow's milk has the capacity to induce tolerance to an unrelated, non-milk, food allergen. Histone acetylation of T cell genes was investigated to assess potential epigenetic regulation. Female C3H/HeOuJ mice were sensitized and challenged to ovalbumin. Prior to sensitization, the mice were treated with raw milk, processed milk, or phosphate-buffered saline for eight days. Allergic symptoms were assessed after challenge and histone modifications in T cell-related genes of splenocyte-derived CD4+ T cells and the mesenteric lymph nodes were analyzed after milk exposure and after challenge. Unlike processed milk, raw milk decreased allergic symptoms. After raw milk exposure, histone acetylation of Th1-, Th2-, and regulatory T cell-related genes of splenocyte-derived CD4+ T cells was higher than after processed milk exposure. After allergy induction, this general immune stimulation was resolved and histone acetylation of Th2 genes was lower when compared to processed milk. Raw milk reduces allergic symptoms to an unrelated, non-milk, food allergen in a murine model for food allergy. The activation of T cell-related genes could be responsible for the observed tolerance induction, which suggested that epigenetic modifications contribute to the allergy-protective effect of raw milk.


Assuntos
Montagem e Desmontagem da Cromatina , Epigênese Genética , Hipersensibilidade Alimentar/dietoterapia , Histonas/metabolismo , Tolerância Imunológica , Ativação Linfocitária , Leite/imunologia , Subpopulações de Linfócitos T/metabolismo , Acetilação , Animais , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Camundongos Endogâmicos C3H , Ovalbumina , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
3.
Nutrients ; 11(7)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31262028

RESUMO

Raw cow's milk was previously shown to suppress allergic symptoms in a murine model for food allergy. In the present study, we investigated the contribution of fat content and heat-sensitive milk components to this allergy-protective effect. In addition, we determined the potency of alkaline phosphatase (ALP), a heat-sensitive raw milk component, to affect the allergic response. C3H/HeOuJ mice were treated with raw milk, pasteurized milk, skimmed raw milk, pasteurized milk spiked with ALP, or phosphate-buffered saline for eight days prior to sensitization and challenge with ovalbumin (OVA). Effects of these milk types on the allergic response were subsequently assessed. Similar to raw milk, skimmed raw milk suppressed food allergic symptoms, demonstrated by a reduced acute allergic skin response and low levels of OVA-specific IgE and Th2-related cytokines. This protective effect was accompanied by an induction of CD103+CD11b+ dendritic cells and TGF-ß-producing regulatory T cells in the mesenteric lymph nodes. Pasteurized milk was not protective but adding ALP restored the allergy-protective effect. Not the fat content, but the heat-sensitive components are responsible for the allergy-protective effects of raw cow's milk. Adding ALP to heat-treated milk might be an interesting alternative to raw cow's milk consumption, as spiking pasteurized milk with ALP restored the protective effects.


Assuntos
Fosfatase Alcalina/imunologia , Dermatite Atópica/prevenção & controle , Manipulação de Alimentos/métodos , Hipersensibilidade Alimentar/prevenção & controle , Proteínas do Leite/imunologia , Pasteurização , Animais , Basófilos/imunologia , Basófilos/metabolismo , Células Cultivadas , Citocinas/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Imunoglobulinas/sangue , Lipídeos/imunologia , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos Endogâmicos C3H , Ovalbumina , Desnaturação Proteica , Pele/imunologia , Pele/metabolismo , Baço/imunologia , Baço/metabolismo
4.
Cells ; 8(6)2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174293

RESUMO

Food allergies are a steadily increasing health and economic problem. Immunologically, food allergic reactions are caused by pathological, allergen-specific Th2 responses resulting in IgE-mediated mast cell degranulation and associated inflammatory reactions. Clinically, food allergies are characterized by local inflammation of the mouth mucosa, the face, the throat, the gastrointestinal tract, are frequently paralleled by skin reactions, and can result in life-threatening anaphylactic reactions. To better understand food allergies and establish novel treatment options, mouse models are indispensable. This review discusses the available mouse food allergy models, dividing them into four categories: (1) adjuvant-free mouse models, (2) mouse models relying on adjuvants to establish allergen-specific Th2 responses, (3) mouse models using genetically-modified mouse strains to allow for easier sensitization, and (4) humanized mouse models in which different immunodeficient mouse strains are reconstituted with human immune or stem cells to investigate humanized immune responses. While most of the available mouse models can reproducibly portray the immunological parameters of food allergy (Th2 immune responses, IgE production and mast cell activation/expansion), so far, the recreation of the clinical parameters has proven more difficult. Therefore, up to now none of the available mouse models can reproduce the complete human pathology.


Assuntos
Hipersensibilidade Alimentar/patologia , Adjuvantes Imunológicos/metabolismo , Alérgenos/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/metabolismo , Camundongos , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
5.
Int Arch Allergy Immunol ; 180(1): 10-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31234191

RESUMO

BACKGROUND: Shrimp-derived allergen has a serious impact on people's health. Chitosan oligosaccharide (COS) has anti-allergic action but its function on shrimp allergen-induced allergy and related molecular mechanisms remain unclear. METHODS: COS and its degrees of polymerization (DP) were selected to interact with shrimp tropomyosin (TM) and IgE was measured. A mouse model of food allergy was established by receiving shrimp TM intraperitoneally. The models were treated with different concentrations of COS. Fecal and serum histamine, serum IgE, IgG1 and IgG2a, and inflammatory cytokines were measured. RESULTS: The main products for COS were DP2-6 with the contents of 6, 40, 26, 16, and 4%, respectively, and reacted with shrimp TM increasingly when COS DP was increased. Severe symptoms of food allergy were observed in the TM group (diarrhea, anaphylactic response, and rectal temperature). In contrast, COS treatment improved these symptoms significantly (p < 0.05). The sensitized mice were desensitized after they were treated with 1 mg/kg COS. COS treatment significantly reduced serum IgE and IgG1 levels, and increased IgG2a levels (p < 0.05). COS consumption decreased fecal and serum histamine. COS treatment reduced Th2 cytokine (IL-4, IL-5, and IL-13) levels and increased the Th1 cytokine (IFN-γ) level (p < 0.05). CONCLUSIONS: COS showed anti-allergy properties by regulating the levels of Th1 and Th2 cytokines.


Assuntos
Alérgenos/imunologia , Antialérgicos/farmacologia , Quitosana , Crustáceos , Hipersensibilidade Alimentar/imunologia , Oligossacarídeos/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Tropomiosina/imunologia , Animais , Antialérgicos/química , Quitosana/química , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/metabolismo , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Oligossacarídeos/química , Fenótipo , Células Th1/metabolismo , Células Th2/metabolismo
6.
J Nutr Sci Vitaminol (Tokyo) ; 65(2): 113-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061279

RESUMO

Food allergy prevalence is increasing all over the world. Recent epidemiologic studies have shown the link between vitamin D3 insufficiency and food allergy occurrence. In this study, we investigated the effect of supplementation with cholecalciferol, a widely used form of vitamin D3, on food allergy using an experimental mouse model. In wild-type BALB/c mice which were sensitized and challenged with an experimental allergen, ovalbumin, a clinical symptom of food allergy, diarrhea, was significantly induced with the elevation of immunoglobulin E level and the increases of T helper 2 cytokine productions, such as interleukin-4, -5, and -13 (p<0.05), whereas no change in T helper 1 cytokine production, such as interferon-γ, was observed. It was also found that cell population of CD69+ CD4+ T cells was increased slightly in spleen and significantly in the mesenteric lymphnode with the diarrheal symptom (p<0.05). Treatment of cholecalciferol reduced the allergic diarrhea (p<0.05) with the decreasing tendency of CD69+ CD4+ T cells, suggesting that the cell population might be associated with the attenuating effect of cholecalciferol on diarrhea occurrence, although immunoglobulin E levels and cytokine productions were not significantly altered by the treatment of cholecalciferol. When given the mice anti-CD69 mAb treatment, significant improvement of allergic diarrhea symptom was observed (p<0.05), accompanying the decrease of CD69+ CD4+ T cells which suggested the contribution of these cells to the diarrhea symptom. Taken together, we suggest that administration of cholecalciferol might be useful to suppress symptomatic food allergy in association with the decrease of CD69+ CD4+ T cells.


Assuntos
Antígenos CD , Antígenos de Diferenciação de Linfócitos T , Linfócitos T CD4-Positivos , Colecalciferol/farmacologia , Hipersensibilidade Alimentar , Lectinas Tipo C , Animais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Citocinas/análise , Citocinas/metabolismo , Diarreia/imunologia , Diarreia/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo
7.
Gastroenterology ; 157(1): 109-118.e5, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31100380

RESUMO

BACKGROUND & AIMS: Confocal laser endomicroscopy (CLE) is a technique that permits real-time detection and quantification of changes in intestinal tissues and cells, including increases in intraepithelial lymphocytes and fluid extravasation through epithelial leaks. Using CLE analysis of patients with irritable bowel syndrome (IBS), we found that more than half have responses to specific food components. Exclusion of the defined food led to long-term symptom relief. We used the results of CLE to detect reactions to food in a larger patient population and analyzed duodenal biopsy samples and fluid from patients to investigate mechanisms of these reactions. METHODS: In a prospective study, 155 patients with IBS received 4 challenges with each of 4 common food components via the endoscope, followed by CLE, at a tertiary medical center. Classical food allergies were excluded by negative results from immunoglobulin E serology analysis and skin tests for common food antigens. Duodenal biopsy samples and fluid were collected 2 weeks before and immediately after CLE and were analyzed by histology, immunohistochemistry, reverse transcription polymerase chain reaction, and immunoblots. Results from patients who had a response to food during CLE (CLE+) were compared with results from patients who did not have a reaction during CLE (CLE-) or healthy individuals (controls). RESULTS: Of the 108 patients who completed the study, 76 were CLE+ (70%), and 46 of these (61%) reacted to wheat. CLE+ patients had a 4-fold increase in prevalence of atopic disorders compared with controls (P = .001). Numbers of intraepithelial lymphocytes were significantly higher in duodenal biopsy samples from CLE+ vs CLE- patients or controls (P = .001). Expression of claudin-2 increased from crypt to villus tip (P < .001) and was up-regulated in CLE+ patients compared with CLE- patients or controls (P = .023). Levels of occludin were lower in duodenal biopsy samples from CLE+ patients vs controls (P = .022) and were lowest in villus tips (P < .001). Levels of messenger RNAs encoding inflammatory cytokines were unchanged in duodenal tissues after CLE challenge, but eosinophil degranulation increased, and levels of eosinophilic cationic protein were higher in duodenal fluid from CLE+ patients than controls (P = .03). CONCLUSIONS: In a CLE analysis of patients with IBS, we found that more than 50% of patients could have nonclassical food allergy, with immediate disruption of the intestinal barrier upon exposure to food antigens. Duodenal tissues from patients with responses to food components during CLE had immediate increases in expression of claudin-2 and decreases in occludin. CLE+ patients also had increased eosinophil degranulation, indicating an atypical food allergy characterized by eosinophil activation.


Assuntos
Alérgenos , Claudina-2/metabolismo , Citocinas/metabolismo , Duodeno/patologia , Proteína Catiônica de Eosinófilo/metabolismo , Hipersensibilidade Alimentar/patologia , Linfócitos Intraepiteliais/patologia , Síndrome do Intestino Irritável/patologia , Ocludina/metabolismo , Adolescente , Adulto , Idoso , Animais , Biópsia , Degranulação Celular , Duodeno/metabolismo , Hipersensibilidade a Ovo/metabolismo , Hipersensibilidade a Ovo/patologia , Clara de Ovo , Endoscopia do Sistema Digestório , Eosinófilos/metabolismo , Feminino , Hipersensibilidade Alimentar/metabolismo , Humanos , Imunoglobulina E , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/metabolismo , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Leite , Hipersensibilidade a Leite/metabolismo , Hipersensibilidade a Leite/patologia , Permeabilidade , Estudos Prospectivos , RNA Mensageiro/metabolismo , Soja , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Triticum , Hipersensibilidade a Trigo/metabolismo , Hipersensibilidade a Trigo/patologia , Leveduras , Adulto Jovem
8.
BMC Bioinformatics ; 20(1): 206, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014233

RESUMO

BACKGROUND: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, concerns with regards to safety and long-term efficacy of OIT remain. There is a need to identify biomarkers that predict, monitor and/or evaluate the effects of OIT. Here we present a method to select candidate biomarkers for efficacy and safety assessment of OIT using the computational approaches Bayesian networks (BN) and Topological Data Analysis (TDA). RESULTS: Data were used from fructo-oligosaccharide diet-supported OIT experiments performed in 3 independent cow's milk allergy (CMA) and 2 independent peanut allergy (PNA) experiments in mice. Bioinformatical approaches were used to understand the data structure. The BN predicted the efficacy of OIT in the CMA with 86% and indicated a clear effect of scFOS/lcFOS on allergy parameters. For the PNA model, this BN (trained on CMA data) predicted an efficacy of OIT with 76% accuracy and shows similar effects of the allergen, treatment and diet as compared to the CMA model. The TDA identified clusters of biomarkers closely linked to biologically relevant clinical symptoms and also unrelated and redundant parameters within the network. CONCLUSIONS: Here we provide a promising application of computational approaches to a) compare mechanistic features of two different food allergies during OIT b) determine the biological relevance of candidate biomarkers c) generate new hypotheses to explain why CMA has a different disease pattern than PNA and d) select relevant biomarkers for future studies.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade Alimentar , Animais , Biomarcadores , Biologia Computacional , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/terapia , Humanos , Camundongos
9.
Front Immunol ; 10: 191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828329

RESUMO

The dramatic increase in food allergy prevalence and severity globally requires effective strategies. Food allergy derives from a defect in immune tolerance mechanisms. Immune tolerance is modulated by gut microbiota function and structure, and microbiome alterations (dysbiosis) have a pivotal role in the development of food allergy. Environmental factors, including a low-fiber/high-fat diet, cesarean delivery, antiseptic agents, lack of breastfeeding, and drugs can induce gut microbiome dysbiosis, and have been associated with food allergy. New experimental tools and technologies have provided information regarding the role of metabolites generated from dietary nutrients and selected probiotic strains that could act on immune tolerance mechanisms. The mechanisms are multiple and still not completely defined. Increasing evidence has provided useful information on optimal bacterial species/strains, dosage, and timing for intervention. The increased knowledge of the crucial role played by nutrients and gut microbiota-derived metabolites is opening the way to a post-biotic approach in the stimulation of immune tolerance through epigenetic regulation. This review focused on the potential role of gut microbiome as the target for innovative strategies against food allergy.


Assuntos
Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Fatores Etários , Animais , Dieta , Gerenciamento Clínico , Suscetibilidade a Doenças , Disbiose/imunologia , Ácidos Graxos/metabolismo , Hipersensibilidade Alimentar/metabolismo , Humanos , Tolerância Imunológica , Probióticos
10.
Int J Mol Sci ; 20(6)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901853

RESUMO

Allergies are a widespread problem in western countries, affecting a large part of the population, with levels of prevalence increasingly rising due to reasons still not understood. Evidence accumulated in recent years points to an essential role played by ligands of allergen proteins in the sensitization phase of allergies. In this regard, we recently identified the natural ligand of Pru p 3, a lipid transfer protein, a major allergen from peach fruit and a model of food allergy. The ligand of Pru p 3 has been shown to play a key role in the sensitization to peach and to other plant food sources that provoke cross-reactivity in a large proportion of patients allergic to peach. However, the question of which is the binding pose of this ligand in its carrier protein, and how it can be transferred to receptors of the immune system where it develops its function as a coadjuvant was not elucidated. In this work, different molecular dynamics simulations have been considered as starting points to study the properties of the ligand⁻protein system in solution. Besides, an energy landscape based on collective variables that describe the process of ligand motion within the cavity of Pru p 3 was obtained by using well-tempered metadynamics. The simulations revealed the differences between distinct binding modes, and also revealed important aspects of the motion of the ligand throughout its carrier protein, relevant to its binding⁻unbinding process. Our findings are potentially interesting for studying protein⁻ligand systems beyond the specific case of the allergen protein dealt with here.


Assuntos
Antígenos de Plantas/química , Proteínas de Transporte/química , Ligantes , Proteínas de Plantas/química , Antígenos de Plantas/imunologia , Antígenos de Plantas/metabolismo , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo , Difusão , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Humanos , Modelos Moleculares , Conformação Molecular , Proteínas de Plantas/imunologia , Proteínas de Plantas/metabolismo , Ligação Proteica , Prunus persica/efeitos adversos , Relação Estrutura-Atividade
11.
Front Immunol ; 10: 205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809227

RESUMO

Background: Mucosal mast cells (MC) are key players in IgE-mediated food allergy (FA). The evidence on the interaction between gut microbiota, MC and susceptibility to FA is contradictory. Objective: We tested the hypothesis that commensal bacteria are essential for MC migration to the gut and their maturation impacting the susceptibility to FA. Methods: The development and severity of FA symptoms was studied in sensitized germ-free (GF), conventional (CV), and mice mono-colonized with L. plantarum WCFS1 or co-housed with CV mice. MC were phenotypically and functionally characterized. Results: Systemic sensitization and oral challenge of GF mice with ovalbumin led to increased levels of specific IgE in serum compared to CV mice. Remarkably, despite the high levels of sensitization, GF mice did not develop diarrhea or anaphylactic hypothermia, common symptoms of FA. In the gut, GF mice expressed low levels of the MC tissue-homing markers CXCL1 and CXCL2, and harbored fewer MC which exhibited lower levels of MC protease-1 after challenge. Additionally, MC in GF mice were less mature as confirmed by flow-cytometry and their functionality was impaired as shown by reduced edema formation after injection of degranulation-provoking compound 48/80. Co-housing of GF mice with CV mice fully restored their susceptibility to develop FA. However, this did not occur when mice were mono-colonized with L. plantarum. Conclusion: Our results demonstrate that microbiota-induced maturation and gut-homing of MC is a critical step for the development of symptoms of experimental FA. This new mechanistic insight into microbiota-MC-FA axis can be exploited in the prevention and treatment of FA in humans.


Assuntos
Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Microbiota , Animais , Biomarcadores , Degranulação Celular/genética , Degranulação Celular/imunologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Hipersensibilidade Alimentar/patologia , Microbioma Gastrointestinal , Vida Livre de Germes , Metagenoma , Metagenômica/métodos , Camundongos , Microbiota/imunologia , RNA Ribossômico 16S
12.
Br J Nutr ; 120(10): 1117-1121, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30401008

RESUMO

We aimed to assess the possible relationship between food allergy and two key adipokines - leptin and adiponectin - in children with food allergy. A total of forty patients with definite diagnosis of food allergy according to clinical history and specific IgE (sIgE) for food allergens (group I) were enrolled in this pilot study. The control group (group II) included thirty children with no evidence of allergic symptoms. Serum levels of leptin and adiponectin were measured by ELISA. Meanwhile, sIgE was measured for the eight most common food allergens by the immunoblot method in all participants. The median ages in groups I and II were 18·5 and 23·5 months, respectively. The respective Caesarean section rate was 64·9 and 16·7 % in groups I and II (P<0·001). Serum levels of adiponectin were significantly higher in the patient group compared with controls (24·11 (sd 12·14) v. 10·67 (sd 12·23) µg/ml, P<0·001), whereas no statistically meaningful difference was detected in serum leptin concentrations (P=0·92). There was a significant inverse relationship between age and adiponectin levels in group I (P=0·002, r -0·479) and group II (P=0·04, r -0·365), and it was more significant in group I. The most common allergens in the patient group were wheat (52·5 %), hazelnut (52·5 %), cow's milk (50 %) and egg white (30 %). The results of this study suggest an essential link between adiponectin and food allergy that is probably unlikely to be affected by obesity as a confounding factor.


Assuntos
Adiponectina/sangue , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/metabolismo , Leptina/sangue , Alérgenos , Animais , Peso ao Nascer , Estudos de Casos e Controles , Cesárea , Pré-Escolar , Corylus , Citocinas/metabolismo , Hipersensibilidade a Ovo/metabolismo , Clara de Ovo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Inflamação , Masculino , Leite , Hipersensibilidade a Leite/metabolismo , Projetos Piloto , Testes Cutâneos , Triticum
13.
Cell Mol Gastroenterol Hepatol ; 6(3): 356-369.e1, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30182049

RESUMO

Immunoglobulin E-mediated food allergy is rapidly developing into a global health problem. Publicly available therapeutic intervention strategies are currently restricted to allergen avoidance and emergency treatments. To gain a better understanding of the disease pathophysiology so that new therapies can be developed, major research efforts have been put into studying food allergy in mice. Animal models should reflect the human pathology as closely as possible to allow for a rapid translation of basic science observations to the bedside. In this regard, experimental models of food allergy provide significant challenges for research because of discrepancies between the presentation of disease in humans and mice. The goal of this review is to give a summary of commonly used murine disease models and to discuss how they relate to the human condition. We will focus on epicutaneous sensitization models, on mouse strains that sensitize spontaneously to food as seen in humans, and on models in humanized animals. In summary, expanding the research toolbox of experimental food allergy provides an important step toward closing gaps in our understanding of the derailing immune mechanism that underlies the human disease. The availability of additional experimental models will provide exciting opportunities to discover new intervention points for the treatment of food allergies. (Cell Mol Gastroenterol Hepatol 2018;x:x).


Assuntos
Modelos Animais de Doenças , Hipersensibilidade Alimentar/metabolismo , Alimentos/efeitos adversos , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Hipersensibilidade Alimentar/imunologia , Humanos , Imunização , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Receptores de IgE/genética , Receptores de IgE/imunologia
14.
Food Funct ; 9(9): 4897-4905, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30168566

RESUMO

The aim of this study was to develop an effective method for decreasing the content of histamine and the immunoreactivity of parvalbumin in Decapterus maruadsi. As demonstrated by reverse phase high performance liquid chromatography, no effect on histamine content was found when fish were treated by boiling (100 °C), ultrasonication, ultraviolet irradiation, pressure treatment (121 °C, 0.12 MPa). However, the histamine content was reduced by 73.55% when the Maillard reaction was combined with pressure treatment (MPT). Further, the allergenicity of parvalbumin was retained after boiling, ultrasonication and ultraviolet irradiation, but was effectively decreased when fish were treated by MPT. Animal experimental results showed lower levels of IgE, IgG1 and IgG2a and contents of serum histamine when measured in a group of MPT sensitized mice. These results showed that the MPT is an effective method for simultaneously reducing the histamine content and the immunoreactivity of parvalbumin from Decapterus maruadsi.


Assuntos
Alérgenos/efeitos adversos , Produtos Pesqueiros/efeitos adversos , Proteínas de Peixes da Dieta/efeitos adversos , Manipulação de Alimentos , Hipersensibilidade Alimentar/prevenção & controle , Histamina/efeitos adversos , Parvalbuminas/efeitos adversos , Alérgenos/química , Animais , Linhagem Celular , Células Cultivadas , Feminino , Produtos Pesqueiros/análise , Proteínas de Peixes da Dieta/química , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Histamina/análise , Temperatura Alta , Humanos , Imunoglobulina E/análise , Imunoglobulina E/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/patologia , Reação de Maillard , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Mastócitos/patologia , Camundongos Endogâmicos BALB C , Parvalbuminas/química , Perciformes , Pressão , Estabilidade Proteica , Ratos , Organismos Livres de Patógenos Específicos , Baço/imunologia , Baço/metabolismo , Baço/patologia
16.
Allergy ; 73(11): 2137-2149, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30028518

RESUMO

BACKGROUND: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics. METHODS: Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis. RESULTS: We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism. CONCLUSION: We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.


Assuntos
Biomarcadores , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/metabolismo , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/metabolismo , Alimentos/efeitos adversos , Genômica , Metabolômica , Plaquetas/metabolismo , Hiper-Reatividade Brônquica/diagnóstico , Cromatografia Líquida , Biologia Computacional/métodos , Feminino , Hipersensibilidade Alimentar/diagnóstico , Cromatografia Gasosa-Espectrometria de Massas , Perfilação da Expressão Gênica , Genômica/métodos , Humanos , Masculino , Espectrometria de Massas , Metaboloma , Metabolômica/métodos , Fenótipo , Índice de Gravidade de Doença
18.
Int J Mol Sci ; 19(5)2018 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-29757238

RESUMO

In contrast with Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. One difficulty in the identification of universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Such responses are launched against harmful macroscopic parasites and noxious substances, such as venoms, but also against largely innocuous allergens. This suggests that the established understanding about sense and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters, which can activate or lower the threshold activation of the immune system, are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that forms an adaptive Th2 response.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Imunidade , Células Th2/imunologia , Células Th2/metabolismo , Animais , Humanos , Imunização , Imunoglobulina E/imunologia
19.
Clin Exp Allergy ; 48(9): 1147-1154, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29746003

RESUMO

BACKGROUND: We have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle-aged adults and in young subjects with asthma. OBJECTIVE: To investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics. METHODS: FeNO, urinary eosinophil-derived neurotoxin (U-EDN), serum eosinophil cationic protein (S-ECP) and periostin were measured in 396 asthmatics, aged 17-76 years, from the Swedish GA2LEN study. Sensitization to airborne allergens was examined with skin prick tests (≥3 mm wheal) and sensitization to food allergens with measurement of specific IgE (≥0.35 kU/L). RESULTS: Asthmatics sensitized to food allergens had higher FeNO, 22.3 ppb (18.6, 26.7) vs 16.1 ppb (14.2, 18.2) (P = .005), S-ECP, 17.7 mg/L (14.8, 21.1) vs 12.8 mg/L (10.9, 14.9) (P = .01), and periostin, 73.7 (67.5, 80.3) ng/mL vs 59.9 (55.8, 64.2) ng/mL (P = .003), than non-sensitized subjects. Periostin levels in this group were also significantly higher than in the group sensitized only to airborne allergens (P = .01). Sensitization to food allergens related independently to FeNO (P = .02), S-ECP (P = .006) and periostin (P = .004), whereas sensitization only to airborne allergens related only to FeNO (P = .02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S-ECP (r = .17, P < .001), periostin (r = .19, P < .001) and U-EDN (0.16, P < .001). S-ECP also correlated weakly with U-EDN (r = .12, P = .02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant. CONCLUSIONS & CLINICAL RELEVANCE: Sensitization to food allergens related to several local and systemic type 2 inflammation markers, such as FeNO, S-ECP and periostin. Assessing the profile of allergic sensitization, including to food allergens, might improve the understanding and interpretation of inflammatory markers and potentially improve asthma management.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Asma/metabolismo , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Alimentos/efeitos adversos , Imunoglobulina E/imunologia , Adulto , Asma/diagnóstico , Biomarcadores , Testes Respiratórios , Expiração , Feminino , Hipersensibilidade Alimentar/diagnóstico , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Óxido Nítrico , Testes de Função Respiratória , Testes Cutâneos , Espirometria
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