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1.
Methods Mol Biol ; 2223: 1-17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226583

RESUMO

Mouse models of allergic disease offer numerous advantages when compared to the models of other animals. However, selection of appropriate mouse models is critical to advance the field of food allergy by revealing mechanisms of allergy and for testing novel therapeutic approaches. All current mouse models for food allergy have weaknesses that may limit their applicability to human disease. Aspects such as the genetic predisposition to allergy or tolerance from the strain of mouse used, allergen dose, route of exposure (oral, intranasal, intraperitoneal, or epicutaneous), damage of the epithelial barrier, use of adjuvants, food matrix effects, or composition of the microbiota should be considered prior to the selection of a specific murine model and contemplated according to the intended purpose of the study. This chapter reviews our current knowledge on the application of mouse models to food allergy research and the variables that may influence the successful development of each type of model.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Alérgenos/administração & dosagem , Modelos Animais de Doenças , Hipersensibilidade Alimentar/imunologia , Regulação da Expressão Gênica/imunologia , Alérgenos/química , Animais , Toxinas Bacterianas/administração & dosagem , Misturas Complexas/administração & dosagem , Misturas Complexas/química , Vias de Administração de Medicamentos , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/patologia , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Knockout , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Especificidade da Espécie , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia
2.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375120

RESUMO

Shellfish allergy affects 2% of the world's population and persists for life in most patients. The diagnosis of shellfish allergy, in particular shrimp, is challenging due to the similarity of allergenic proteins from other invertebrates. Despite the clinical importance of immunological cross-reactivity among shellfish species and between allergenic invertebrates such as dust mites, the underlying molecular basis is not well understood. Here we mine the complete transcriptome of five frequently consumed shrimp species to identify and compare allergens with all known allergen sources. The transcriptomes were assembled de novo, using Trinity, from raw RNA-Seq data of the whiteleg shrimp (Litopenaeus vannamei), black tiger shrimp (Penaeus monodon), banana shrimp (Fenneropenaeus merguiensis), king shrimp (Melicertus latisulcatus), and endeavour shrimp (Metapenaeus endeavouri). BLAST searching using the two major allergen databases, WHO/IUIS Allergen Nomenclature and AllergenOnline, successfully identified all seven known crustacean allergens. The analyses revealed up to 39 unreported allergens in the different shrimp species, including heat shock protein (HSP), alpha-tubulin, chymotrypsin, cyclophilin, beta-enolase, aldolase A, and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Multiple sequence alignment (Clustal Omega) demonstrated high homology with allergens from other invertebrates including mites and cockroaches. This first transcriptomic analyses of allergens in a major food source provides a valuable resource for investigating shellfish allergens, comparing invertebrate allergens and future development of improved diagnostics for food allergy.


Assuntos
Alérgenos/genética , Proteínas de Artrópodes/genética , Hipersensibilidade Alimentar/genética , Perfilação da Expressão Gênica/métodos , Penaeidae/genética , Transcriptoma/genética , Alérgenos/imunologia , Animais , Proteínas de Artrópodes/classificação , Proteínas de Artrópodes/imunologia , Reações Cruzadas/imunologia , Evolução Molecular , Hipersensibilidade Alimentar/imunologia , Humanos , Penaeidae/classificação , Penaeidae/imunologia , Filogenia , Alimentos Marinhos/análise , Especificidade da Espécie , Tropomiosina/genética , Tropomiosina/imunologia
3.
Zhonghua Er Ke Za Zhi ; 58(7): 559-563, 2020 Jul 02.
Artigo em Chinês | MEDLINE | ID: mdl-32605339

RESUMO

Objective: To investigate the relationship between gene polymorphism of rs2228055 locus in the exon region of interleukin-10 receptor A (IL-10RA) and susceptibility to food allergy in children. Methods: This was a case-control study. The food allergy group had 150 children who were diagnosed with food allergy in the Pediatric Food Allergy Clinic of Peking University Third Hospital from August 1, 2017 to November 30, 2018. Another 150 healthy children attended Child Health and Development Center in the same hospital were selected as control group. The genotypes of rs2228055 locus in both groups were detected by PCR re-sequencing. And the genotypes and allele frequencies of rs2228055 locus were compared between these two groups, as well as between food allergy children with positive and negative allergen specific IgE, and between those with and without involvement of different organs. Using the computer virtual mutation to stimulate the changes of amino acid caused by change of rs2228055 locus allele, to analyze the effect of amino acid changes on the structure of IL-10RA. The chi-square test was used for comparison between groups. Results: (1) There were 92 males and 58 females in food allergy group, and 86 males and 64 females in control group, without any statistically significant difference (χ(2)=0.497, P=0.481). The ages of the two groups were 4.2 (0.1-15.0) and 8.0 (0.1-14.0) years old, respectively, the difference was statistically significant (Z=-6.109, P<0.01). (2) The genotype frequencies of rs2228055 locus in the food allergy group and the control group were as follows: AA accounted for 73 (48.7%) and 98 (65.3%), AG accounted for 62 (41.3%) and 42 (28.0%), and GG accounted for 15 (10.0%) and 10 (6.7%), respectively. The allele frequencies in the two groups were as follows: 208 (69.3%) and 238 (79.3%) for A, 92 (30.7%) and 62 (20.7%) for G, respectively. AG and GG genotype frequency and the allele G frequency in food allergy group were significantly higher than that in control group (χ(2)=8.501 and 7.862, P=0.014 and 0.005, respectively). (3) There were no significant differences in genotype frequencies and allele frequencies of rs2228055 locus of allergen-specific IgE-positive and negative food allergy children (all P>0.05). (4) There were no significant differences in genotype frequencies and allele frequencies of rs2228055 locus in the manifestations of skin, digestive system and respiratory system in food allergy children (all P>0.05). (5) The computer virtual mutation showed that the mutation energy was -0.08 without any increase in the stability of IL-10RA when the amino acid encoded by rs2228055 locus was changed from isoleucine to valine. Conclusions: The frequencies of genotype AG, GG and allele G of rs2228055 locus in the IL-10RA exon region in food allergy children are higher than that in non-allergic children, and those with the G allele are more likely to develop food allergy.


Assuntos
Hipersensibilidade Alimentar , Predisposição Genética para Doença , Receptores de Interleucina-10 , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Éxons/genética , Feminino , Hipersensibilidade Alimentar/genética , Frequência do Gene , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-10/genética
4.
Adv Exp Med Biol ; 1253: 141-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32445094

RESUMO

Food allergy is a global health problem, particularly in developed countries. It is mainly mediated by Th2 cell and IgE produced by B cells. While the pathogenesis of IgE-mediated food allergy is quite straightforward, the factors that lead to the development of food allergies at any age in children and adults are unclear. Recent studies have revealed that genetics, epigenetics, and environmental exposures contribute to the development of atopy. In this chapter, we discuss the interplay between these three key elements, reveal how epigenetic modifications may mediate genetic susceptibility of food allergies, and explain why epigenetic modifications may be the key in environmental factors mediated-gene expression, leading to the loss of immune tolerance and eventually, the initiation of food allergies. It should be noted that the study of the role of epigenetics in food allergy is still in its infancy, and lags behind research on epigenetics in other fields such as cancer and autoimmune diseases. One of the reasons for this may be the extreme complexity and variability of clinical presentation of food allergy, ranging from less severe forms such as oral allergy syndrome to full-blown anaphylaxis. Research on early exposure has disrupted the previous thinking of avoidance of food allergies to prevent sensitization in children, instead leading to recommendations that early introduction to foods may, in fact, induce tolerance. However, clear and unequivocal guidelines on how to approach this in the clinical setting have not been developed. The coming of the epigenetic era in food allergies is to provide better understanding of pathogenesis of food allergy, as well as providing therapeutic and preventive strategies for this very common condition.


Assuntos
Epigênese Genética , Epigenômica , Hipersensibilidade Alimentar/genética , Humanos , Tolerância Imunológica
6.
Int Arch Allergy Immunol ; 181(3): 200-210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31865311

RESUMO

INTRODUCTION: Genetic polymorphisms associated with IgE-mediated food sensitization have been a robust area of research for decades. A genome-wide search for susceptible loci regulating the IgE response (atopy) identified the candidate gene STAT6, which is important in the context of food allergic manifestations. OBJECTIVE: The present study was designed to investigate the sensitization of West Bengal population against some common allergenic food items and to study the role of the STAT6 gene polymorphism in elevating food-specific IgE levels among sensitized individuals. METHODS: Skin prick test was performed for 6 food items among 501 patients (126 children, 85 adolescents, and 290 adults)from West Bengal, India. Among them, 165 patients were selected for measurement of total IgE and food-specific IgE levels along with 165 controls. Finally, the STAT6 (rs3024974 (C/T) polymorphism was genotyped in 139 cases and control subjects. RESULTS: Shrimp was identified as a dominant food allergen in adolescents and adults, whereas milk sensitization was highest in children. Food-sensitized patients with onset during childhood had significantly higher total IgE levels compared to patients with onset during adulthood (p < 0.00001). The frequency of the rs3024974 CC genotype in both cases and control subjects (55.40 and 46.76%, respectively) was higher than that of CT or TT. Patients with childhood onset bearing the CC genotype had significantly higher specific IgE levels in comparison to those with adult onset (p = 0.001). CONCLUSION: Food sensitization has a genetic background and the rs3024974 polymorphism is associated with susceptibility and reaction severity in food-sensitized patients in West Bengal population in India.


Assuntos
Hipersensibilidade Alimentar/genética , Genótipo , Fator de Transcrição STAT6/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Imunoglobulina E/metabolismo , Índia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
7.
Biomolecules ; 9(12)2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810340

RESUMO

Impairment of the intestinal barrier is one of the key events in the initiation of the sensitization process in food allergy. The aim of this study was to explore the effects of kiwifruit allergen Act d 1 on intestinal permeability and tight junction protein (TJP) gene expression in vivo and to explore its potential to activate the NF-ĸB signaling pathway and to regulate expression of epithelial pro-allergenic cytokines. Influences of Act d 1 on TJP gene expression and pro-allergenic cytokines in the mouse intestine was analyzed by qPCR upon allergen administration by oral gavage. The effect on the in vivo intestinal permeability was assessed in ELISA by measuring the translocation of ß-lactoglobulin (BLG) into circulation. The capacity of Act d 1 to activate the NF-ĸB pathway was tested in HEK293 cells by fluorescent microscopy and flow cytometry. Administration of Actinidin (Act d 1) increased intestinal permeability to the BLG. This was accompanied by changes in gene expression of TJP mRNA and pro-allergenic cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) compared to the control. Act d 1 reduced TEER of the HEK293 monolayer, was positive in an NF-ĸB-reporter HEK293 cell assay, and induced secretion of TSLP. These findings shed more light on the molecular events in the sensitization process of kiwifruit but possibly also of other protease food allergens.


Assuntos
Actinidia/imunologia , Antígenos de Plantas/administração & dosagem , Citocinas/genética , Hipersensibilidade Alimentar/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas de Junções Íntimas/genética , Animais , Antígenos de Plantas/imunologia , Antígenos de Plantas/farmacologia , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lactoglobulinas/metabolismo , Camundongos , NF-kappa B/metabolismo , Permeabilidade
8.
Int Arch Allergy Immunol ; 180(4): 235-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31694044

RESUMO

Over the last decades, an increasing appearance of allergies and atopic disorders, such as asthma, dermatitis, and rhinitis, has been observed. The mechanisms of these disorders remain unclear, and therefore the development of novel therapies is limited. Current treatments are often symptomatic, nonspecific, or may have severe side effects. Further insights into the mechanisms of the underlying disease pathogenesis could reveal novel targets for treatment. In this review, we provide an update on recent basic and translational studies that offer novel insights and opportunities for the treatment of patients with atopic disorders.


Assuntos
Asma/etiologia , Dermatite Atópica/etiologia , Hipersensibilidade Alimentar/etiologia , Rinite Alérgica/etiologia , Alérgenos/imunologia , Asma/genética , Asma/terapia , Dermatite Atópica/genética , Dermatite Atópica/terapia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/terapia , Predisposição Genética para Doença/genética , Humanos , Rinite Alérgica/genética , Rinite Alérgica/terapia , Fatores de Risco
9.
Immunobiology ; 224(6): 804-810, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31471097

RESUMO

The immune regulatory cell dysfunction is associated with many immune diseases including food allergy (FA). This study aims to investigate the role of vasoactive intestinal peptide (VIP) in the maintenance of regulatory B cell (Br cell)'s immune suppressive functions by stabilizing thrombospondin (TSP1) expression. In this study, blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. Br cells were isolated from the samples through flow cytometry cell sorting and analyzed by immunological approaches to determine the immune regulatory capacity. We found that the immune suppressive functions of Br cells were impaired in FA patients. The serum VIP levels were associated with the production of immune suppressive function-related mediators (interleukin-10, IL-10) of Br cells in FA patients. VIP counteracted IL-10 mRNA decay in Br cells by up regulating the TSP1 expression. TSP1 inhibited tristetraprolin (TTP) to prevent IL-10 mRNA decay in Br cells. Administration of VIP inhibited FA response through restoration of immune suppressive functions in Br cells. In conclusion, administration of VIP can alleviate FA response through up regulating expression of TSP1 to stabilize IL-10 expression in FA Br cells and recover the immune regulatory functions. The results have translational potential for the treatment of FA and other disorders associated with immune regulatory dysfunction of Br cells.


Assuntos
Linfócitos B Reguladores/imunologia , Hipersensibilidade Alimentar/imunologia , Interleucina-10/imunologia , Peptídeo Intestinal Vasoativo/imunologia , Adulto , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/imunologia , Feminino , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/genética , Humanos , Interleucina-10/genética , Masculino , Camundongos Endogâmicos BALB C , Peptídeo Intestinal Vasoativo/sangue , Adulto Jovem
10.
Eur J Pediatr ; 178(10): 1507-1517, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414213

RESUMO

The prevalence of allergic diseases in children is markedly increasing to epidemic proportions. The aim of this study is to describe the presence and examine associated parental and child characteristics of allergic sensitization and physician-diagnosed allergy in Dutch children at age 10 years. This study among 5471 children was performed in a population-based prospective cohort from fetal life onwards. Allergic sensitization was measured by skin prick tests. Physician-diagnosed allergy and parental and child characteristics were collected by questionnaires. In children aged 10 years, inhalant and food allergic sensitization was present in 32.2% and 7.1%, and physician-diagnosed inhalant and food allergy in 12.4% and 2.3%. Maternal and paternal history of allergy, eczema or asthma was associated with increased risks of physician-diagnosed inhalant allergy (aOR (95% CI) 1.44 (1.23-1.70) and 1.59 (1.30-1.94), respectively), but not with food allergy. Asthma and eczema ever at age 10 years were associated with increased risks of physician-diagnosed inhalant allergy (4.60 (3.55-5.96) and 2.42 (1.94-3.03), respectively). Eczema ever at age 10 years was associated with an increased risk of physician-diagnosed food allergy (5.78, 3.04-9.52), with the highest risk of cashew (7.36, 3.20-16.94) and peanut (5.58, 3.08-10.10) food allergy.Conclusions: We found strong effects of parental history of allergy, eczema or asthma on the presence of physician-diagnosed inhalant allergy in children at age 10 years. Eczema ever at age 10 years was a strong risk factor for the development of physician-diagnosed inhalant and food allergy. What is Known: • The prevalence of allergic diseases in children has markedly increased. • Early-life influences are critically important in the development of allergic diseases. What is New: • Maternal and paternal history of allergy, eczema or asthma is associated with increased risks of physician-diagnosed inhalant allergy but not with food allergy. • Eczema ever at age 10 years is associated with an increased risk of physician-diagnosed food allergy, with the highest risk for cashew and peanut food allergy.


Assuntos
Asma/epidemiologia , Eczema/epidemiologia , Hipersensibilidade Alimentar/genética , Adulto , Asma/diagnóstico , Asma/genética , Criança , Estudos Transversais , Eczema/diagnóstico , Eczema/genética , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Países Baixos/epidemiologia , Pais , Gravidez , Estudos Prospectivos , Inquéritos e Questionários
11.
Theranostics ; 9(17): 4982-4992, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410196

RESUMO

Rationale: Mast cells play a crucial role in allergic diseases. Yet, the regulation of mast cell bioactivities is not fully understood. This study aims to elucidate the role of B cell lymphoma 2 like protein 12 (Bcl2L12), one of the anti-apoptosis proteins, in regulating mast cell apoptosis. Methods: A food allergy (FA) mouse model was developed to establish mast cell over population in the intestinal tissue. Either compound 48/80 (C48/80) or specific antigens were used to activate mast cells in the intestinal mucosa. Results: After treating with C48/80, apoptosis was induced in mast cells of the intestine of naive control mice, but not in FA mice. The expression of Fas ligand (FasL) was lower in the mast cells of FA mice. Interleukin (IL)-5 was responsible for the suppression of FasL by upregulating the expression of Bcl2L12 in mast cells. Bcl2L12 prevented c-Myc, the major transcription factor of FasL, from binding the FasL promoter to inhibit the expression of FasL in mast cells. Inhibition of Bcl2L12 restored the apoptosis machinery of mast cells in the FA mouse intestine. Conclusions: The apoptosis machinery in mast cells is impaired in an allergic environment. Inhibition of Bcl2L12 restores the apoptosis machinery in mast cells in the FA mouse intestine.


Assuntos
Hipersensibilidade Alimentar/metabolismo , Mastócitos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Apoptose , Células Cultivadas , Proteína Ligante Fas/metabolismo , Hipersensibilidade Alimentar/genética , Interleucina-5/genética , Interleucina-5/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo
12.
J Sci Food Agric ; 99(15): 7008-7015, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31435932

RESUMO

BACKGROUND: Silkworm droppings have long been used in traditional medicine to remedy allergic itching, palsy, blood circulation problems, and arthritis in Asian countries. To investigate the anti-allergic effect of silkworm dropping extract (SDE) and its mechanism, we used a mouse model of food allergy induced by ovalbumin (OVA). RESULTS: SDE ameliorated the symptoms of OVA-induced food allergies, and the levels of T helper 2 (Th2)-related cytokines [such as interleukin (IL)-4, IL-5, IL-10, and IL-13] were found to be significantly decreased in both the spleen and mesenteric lymph nodes by SDE. Furthermore, SDE treatment directly inhibited OVA permeation, IL-4 production, and degranulation of mast cells; in contrast, immunoglobulin E (IgE) production from B cells was not affected. CONCLUSION: These results suggest that SDE has potential anti-allergic activities, and SDE may be useful in the treatment/prevention of allergic disorders such as food allergies, serving as therapeutic agents. © 2019 Society of Chemical Industry.


Assuntos
Antialérgicos/administração & dosagem , Bombyx/química , Fezes/química , Hipersensibilidade Alimentar/tratamento farmacológico , Células Th2/efeitos dos fármacos , Animais , Antialérgicos/química , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Células Th2/imunologia
13.
Nutrients ; 11(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284450

RESUMO

This review discusses the personalised dietary approach with respect to inflammatory bowel disease (IBD). It identifies gene-nutrient interactions associated with the nutritional deficiencies that people with IBD commonly experience, and the role of the Western diet in influencing these. It also discusses food intolerances and how particular genotypes can affect these. It is well established that with respect to food there is no "one size fits all" diet for those with IBD. Gene-nutrient interactions may help explain this variability in response to food that is associated with IBD. Nutrigenomic research, which examines the effects of food and its constituents on gene expression, shows that-like a number of pharmaceutical products-food can have beneficial effects or have adverse (side) effects depending on a person's genotype. Pharmacogenetic research is identifying gene variants with adverse reactions to drugs, and this is modifying clinical practice and allowing individualised treatment. Nutrigenomic research could enable individualised treatment in persons with IBD and enable more accurate tailoring of food intake, to avoid exacerbating malnutrition and to counter some of the adverse effects of the Western diet. It may also help to establish the dietary pattern that is most protective against IBD.


Assuntos
Deficiências Nutricionais/dietoterapia , Dieta Ocidental/efeitos adversos , Hipersensibilidade Alimentar/dietoterapia , Doenças Inflamatórias Intestinais/dietoterapia , Nutrigenômica/métodos , Estado Nutricional , Medicina de Precisão/métodos , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Adulto , Animais , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/genética , Deficiências Nutricionais/fisiopatologia , Comportamento Alimentar , Feminino , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/fisiopatologia , Interação Gene-Ambiente , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional/genética , Valor Nutritivo , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
14.
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
15.
Curr Opin Immunol ; 60: 141-147, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31302570

RESUMO

The steep rise in the incidence and prevalence of food allergy (FA) in the last few decades have focused attention of environmental mechanisms which act to promote disease, chief among which is the microbiome. Recent studies have now established the presence of pathogenic dysbiosis in FA that could be precipitated by a variety of environmental insults, including among others antibiotic usage and mode of delivery, that act to subvert the immune regulatory response that enforce tolerance to dietary antigens. A key attribute of this dysbiosis is the loss of Clostridial bacterial species that act to promote the formation of food allergen-specific nascent regulatory T cells in the gut. Significantly, different immunoprotective commensal bacteria, including members of the Clostridiales and Bacteroidales orders act to induce the transcription factor RORγt in nascent Treg cells via an upstream MyD88-dependent mechanism to promote tolerance to dietary antigens. Activation of this axis is disrupted by the dysbiosis, and can be restored by treatment with therapeutic microbiota. These findings highlight the potential for novel microbiota-based approaches to the prevention and treatment of the FA epidemic.


Assuntos
Suscetibilidade a Doenças/imunologia , Hipersensibilidade Alimentar/imunologia , Tolerância Imunológica , Imunomodulação , Microbiota/imunologia , Animais , Disbiose/imunologia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/terapia , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Medicina de Precisão , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
17.
PLoS One ; 14(6): e0218253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216310

RESUMO

BACKGROUND: Current laboratory tests are less than 50% accurate in distinguishing between people who have food allergies (FA) and those who are merely sensitized to foods, resulting in the use of expensive and potentially dangerous Oral Food Challenges. This study presents a purely-computational machine learning approach, conducted using DNA Methylation (DNAm) data, to accurately diagnose food allergies and potentially find epigenetic targets for the disease. METHODS AND RESULTS: An unbiased feature-selection pipeline was created that narrowed down 405,000+ potential CpG biomarkers to 18. Machine-learning models that utilized subsets of this 18-feature aggregate achieved perfect classification accuracy on completely hidden test cohorts (on an 8-fold hidden dataset). Ensemble classification was also shown to be effective for this High Dimension Low Sample Size (HDLSS) DNA methylation dataset. The efficacy of these machine learning classifiers and the 18 CpGs was further validated by their high accuracy on a large number of hidden data permutations, where the samples in the training, cross-validation, and hidden sets were repeatedly randomly allocated. The 18-CpG signature mapped to 13 genes, on which biological insights were collected. Notably, many of the FA-discriminating genes found in this study were strongly associated with the immune system, and seven of the 13 genes were previously associated with FA. CONCLUSIONS: Previous studies have also created highly-accurate classifiers for this dataset, using both data-driven and a priori biological insights to construct a 96-CpG signature. This research builds on previous work because it uses a completely computational approach to obtain a perfect classification accuracy while using only 18 highly discriminating CpGs (0.005% of the total available features). In machine learning, simpler models, as used in this study, are generally preferred over more complex ones (other things being equal). Lastly, the completely data-driven methodology presented in this research eliminates the need for a priori biological information and allows for generalizability to other DNAm classification problems.


Assuntos
Biomarcadores/sangue , Metilação de DNA/genética , Hipersensibilidade a Ovo/sangue , Hipersensibilidade Alimentar/sangue , Arachis/efeitos adversos , Epigênese Genética/genética , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/patologia , Humanos , Lactente , Recém-Nascido , Aprendizado de Máquina , Masculino
18.
Biomed Res Int ; 2019: 1315257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111043

RESUMO

Prenatal environmental exposures are considered to contribute to the development of allergic sensitization by epigenetic mechanisms. The role of histone acetylation in the placenta has not been examined yet. We hypothesized that placental histone acetylation at the promoter regions of allergy-related immune regulatory genes is associated with the development of sensitization to allergens in the child. Histones H3 and H4 acetylation at the promoter regions of 6 selected allergy-related immune regulatory genes was assessed by a chromatin immunoprecipitation assay in 173 term placentas collected in the prospective birth-cohort ALADDIN. The development of IgE sensitization to allergens in the children was followed from 6 months up to 5 years of age. We discovered significant associations of histone acetylation levels with decreased risk of allergic sensitization in 3 genes. Decreased risk of sensitization to food allergens was associated with higher H3 acetylation levels in placentas at the IFNG and SH2B3 genes, and for H4 acetylation in HDAC4. Higher HDAC4 H4 acetylation levels were also associated with a decreased risk of sensitization to aeroallergens. In conclusion, our results suggest that acetylation of histones in placenta has a potential to predict the development of sensitization to allergens in children.


Assuntos
Hipersensibilidade Alimentar/genética , Histona Desacetilases/genética , Interferon gama/genética , Proteínas/genética , Proteínas Repressoras/genética , Acetilação , Proteínas Adaptadoras de Transdução de Sinal , Alérgenos/efeitos adversos , Pré-Escolar , Cromatina/genética , Epigênese Genética/genética , Epigênese Genética/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/patologia , Histona Desacetilases/imunologia , Histonas/genética , Histonas/imunologia , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Interferon gama/imunologia , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Placenta/imunologia , Placenta/patologia , Gravidez , Regiões Promotoras Genéticas/genética , Proteínas/imunologia , Proteínas Repressoras/imunologia
20.
J Allergy Clin Immunol Pract ; 7(7): 2337-2347.e7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930272

RESUMO

BACKGROUND: The increasing incidence of food allergy (FA) can be attributed to interactions between genes and the environment, but these interactions are not yet fully clear. OBJECTIVE: We aimed to evaluate the interaction between infant genetic variations and maternal dietary patterns to identify risk factors in the development of FA. METHODS: We used the Cohort for Childhood Origin of Asthma and allergic diseases birth cohort of 1628 infants, born between 2007 and 2015. Maternal dietary intakes were assessed at 26 weeks of pregnancy using a food frequency questionnaire and grouped according to 5 dietary patterns. Infant cord blood samples were genotyped at 12 loci. RESULTS: Among 1628 infants, 147 (9.0%) were diagnosed with FA based on history. A maternal confectionery diet characterized by a higher intake of baked and sugary products during pregnancy was associated with a higher prevalence of FA (adjusted odds ratio [OR] = 1.517, P = .02); this dietary pattern tended to be higher in trans fat (r = 0.498, P < .001). Development of FA was associated with longer periods of breastfeeding (adjusted OR = 1.792, P = .03), and this dietary pattern was more significantly related to the development of FA in infants with the homozygous TT genotype of CD14 (rs2569190) and more than 1 copy of GSTM1 and GSTT1. CONCLUSIONS: A maternal confectionery diet during pregnancy that majorly consists of baked and sugary products, combined with a longer ensuing period of breastfeeding, may lead to the development of FA, suggesting a harmful effect of trans fats in the infant. Polymorphisms in CD14 and GST in the infant influence FA susceptibility.


Assuntos
Carboidratos da Dieta/efeitos adversos , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/genética , Fenômenos Fisiológicos da Nutrição Materna , Ácidos Graxos Trans/efeitos adversos , Adulto , Aleitamento Materno , Dieta , Feminino , Interação Gene-Ambiente , Variação Genética , Genótipo , Glutationa Transferase/genética , Humanos , Lactente , Receptores de Lipopolissacarídeos/genética , Razão de Chances , Gravidez
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