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1.
J Immunol ; 207(11): 2649-2659, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34732466

RESUMO

Dendritic cells (DCs) are the most specialized APCs that play a critical role in driving Th2 differentiation, but the mechanism is not fully understood. Here we show that vacuolar protein sorting 33B (Vps33B) plays an important role in this process. Mice with Vps33b-specific deletion in DCs, but not in macrophages or T cells, were more susceptible to Th2-mediated allergic lung inflammation than wild-type mice. Deletion of Vps33B in DCs led to enhanced CD4+ T cell proliferation and Th2 differentiation. Moreover, Vps33B specifically restrained reactive oxygen species production in conventional DC1s to inhibit Th2 responses in vitro, whereas Vps33B in monocyte-derived DCs and conventional DC2s was dispensable for Th2 development in asthma pathogenesis. Taken together, our results identify Vps33B as an important molecule that mediates the cross-talk between DCs and CD4+ T cells to further regulate allergic asthma pathogenesis.


Assuntos
Células Dendríticas/imunologia , Hipersensibilidade/imunologia , Inflamação/imunologia , Pyroglyphidae/imunologia , Proteínas de Transporte Vesicular/imunologia , Animais , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos
2.
Nat Commun ; 12(1): 5958, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645820

RESUMO

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/microbiologia , Microbioma Gastrointestinal/imunologia , Tolerância Imunológica , Hipersensibilidade Respiratória/microbiologia , Alérgenos/efeitos adversos , Animais , Bacteroides/isolamento & purificação , Bacteroides/metabolismo , Bifidobacterium longum/isolamento & purificação , Bifidobacterium longum/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Clostridiales/isolamento & purificação , Clostridiales/metabolismo , Alérgenos Animais/efeitos adversos , Alérgenos Animais/imunologia , Ovos/efeitos adversos , Faecalibacterium prausnitzii/isolamento & purificação , Faecalibacterium prausnitzii/metabolismo , Feminino , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Lipopolissacarídeos/biossíntese , Masculino , Leite/efeitos adversos , Leite/imunologia , Nozes/efeitos adversos , Nozes/imunologia , Pólen/química , Pólen/imunologia , Prunus persica/química , Prunus persica/imunologia , Pyroglyphidae/química , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/imunologia , Urease/biossíntese
3.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445491

RESUMO

In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed. There was no effect of infection alone on bronchoalveolar lavage cellular inflammation 15 days post-infection; however, OVA or HDM challenge resulted in increased bronchoalveolar inflammation dominated by eosinophils/neutrophils or neutrophils, respectively. Previously infected mice had higher serum OVA-specific IgE compared with uninfected mice. Mice previously infected, sensitized and challenged with OVA were most responsive to methacholine with respect to airway resistance, while HDM challenge caused significant increases in both tissue damping and tissue elastance regardless of previous infection status. Previous influenza infection was associated with decreased claudin-1 expression in all groups and decreased occludin expression in OVA or HDM-challenged mice. This study demonstrates the importance of the respiratory epithelium in pre-sensitized individuals, where influenza-infection-induced barrier disruption resulted in increased systemic OVA sensitization and downstream effects on lung function.


Assuntos
Hiper-Reatividade Brônquica/tratamento farmacológico , Cloreto de Metacolina/administração & dosagem , Infecções por Orthomyxoviridae/complicações , Ovalbumina/imunologia , Pyroglyphidae/imunologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Hiper-Reatividade Brônquica/etiologia , Claudina-1/metabolismo , Regulação para Baixo , Feminino , Vírus da Influenza A/patogenicidade , Cloreto de Metacolina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Ovalbumina/administração & dosagem , Resultado do Tratamento
4.
Sci Rep ; 11(1): 16300, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381060

RESUMO

Diesel exhaust particles (DEPs), traffic-related air pollutants, are considered environmental factors adversely affecting allergic diseases. However, the immunological basis for the adjuvant effects of DEP in allergic rhinitis (AR) remains unclear. Therefore, this study aimed to investigate the effect of DEP exposure on AR using a mouse model. BALB/c mice sensitized to house dust mite (HDM) were intranasally challenged with HDM in the presence and absence of DEP. Allergic symptom scores, serum total and HDM-specific immunoglobulins (Igs), eosinophil infiltration in the nasal mucosa, cytological profiles in bronchoalveolar lavage fluid (BALF), and cytokine levels in the nasal mucosa and spleen cell culture were analyzed. Mice co-exposed to HDM and DEP showed increased allergic symptom scores compared with mice exposed to HDM alone. Reduced total IgE and HDM-specific IgE and IgG1 levels, decreased eosinophil infiltration in the nasal mucosa, and increased proportion of neutrophils in BALF were found in mice co-exposed to HDM and DEP. Interleukin (IL)-17A level was found to be increased in the nasal mucosa of the co-exposure group compared with that in the HDM-exposed group. The levels of IL-4, IL-13, interferon-γ, IL-25, IL-33, and TSLP expression showed no difference between the groups with and without DEP treatment. Increased expression of IL-17A in the nasal mucosa may contribute to DEP-mediated exacerbation of AR in HDM-sensitized murine AR model.


Assuntos
Alérgenos/imunologia , Interleucina-17/imunologia , Mucosa Nasal/imunologia , Material Particulado/imunologia , Pyroglyphidae/imunologia , Rinite Alérgica/imunologia , Poluentes Atmosféricos/imunologia , Animais , Asma/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade Respiratória/imunologia
5.
J Toxicol Environ Health A ; 84(22): 922-931, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34304725

RESUMO

Atopic dermatitis is a chronic inflammatory skin disease, of which incidence is closely related to exposure to environmental pollutants and allergens. Thymic stromal lymphopoietin (TSLP) plays an important role in the early stages of atopic dermatitis development by inducing Th2 immune responses. In addition, TSLP regulates activation of group 2 innate lymphoid cells (ILC2), promoting the pathogenesis of atopic dermatitis. The aim of this study was to investigate whether celastrol alleviated atopic dermatitis symptoms by regulating TSLP expression and ILC2 stimulation. Celastrol suppressed TSLP production in mouse keratinocyte cells by inhibiting NF-ĸB activation. Topical application of celastrol significantly improved atopic dermatitis symptoms induced by house dust mite (HDM) in NC/Nga mice as determined by dermatitis score and histological assessment. Celastrol decreased the levels of TSLP in atopic dermatitis skin lesions of HDM-stimulated NC/Nga mice. Celastrol reduced levels of Th2 cytokines including IL-4, IL-5, and IL-13 in atopic dermatitis skin lesions of NC/Nga mice. Further, celastrol significantly reduced ILC2 population in atopic dermatitis skin lesions of NC/Nga mice. These results indicate that topical application of celastrol improved atopic dermatitis symptoms by lowering TSLP levels and concomitant immune responses. Data demonstrated that reduced TSLP levels and associated lower number of ILC2 cells alleviate atopic dermatitis symptoms induced by house dust mite.


Assuntos
Citocinas/imunologia , Dermatite Atópica/tratamento farmacológico , Linfócitos/efeitos dos fármacos , Triterpenos Pentacíclicos/administração & dosagem , Alérgenos/efeitos adversos , Alérgenos/imunologia , Animais , Linhagem Celular Tumoral , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Modelos Animais de Doenças , Imunidade Inata/efeitos dos fármacos , Inflamação , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Linfócitos/imunologia , Camundongos , NF-kappa B/imunologia , Triterpenos Pentacíclicos/farmacologia , Pyroglyphidae/imunologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia
6.
Mol Immunol ; 137: 238-246, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293591

RESUMO

GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.


Assuntos
Asma/imunologia , Proteína Relacionada a TNFR Induzida por Glucocorticoide/imunologia , Hipersensibilidade/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Pyroglyphidae/imunologia , Fatores de Necrose Tumoral/imunologia , Animais , Dermatophagoides pteronyssinus/imunologia , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Hipersensibilidade Respiratória/imunologia , Transdução de Sinais/imunologia
7.
Biochem Pharmacol ; 192: 114690, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274356

RESUMO

BACKGROUND: Eosinophilic asthma is increasingly recognized as one of the most severe and difficult-to-treat asthma subtypes. The JAK/STAT pathway is the principal signaling mechanism for a variety of cytokines and growth factors involved in asthma. However, the direct effect of JAK inhibitors on eosinophil effector function has not been addressed thus far. OBJECTIVE: Here we compared the effects of the JAK1/2 inhibitor baricitinib and the JAK3 inhibitor tofacitinib on eosinophil effector function in vitro and in vivo. METHODS: Differentiation of murine bone marrow-derived eosinophils. Migratory responsiveness, respiratory burst, phagocytosis and apoptosis of human peripheral blood eosinophils were assessed in vitro. In vivo effects were investigated in a mouse model of acute house dust mite-induced airway inflammation in BALB/c mice. RESULTS: Baricitinib more potently induced apoptosis and inhibited eosinophil chemotaxis and respiratory burst, while baricitinib and tofacitinib similarly affected eosinophil differentiation and phagocytosis. Of the JAK inhibitors, oral application of baricitinib more potently prevented lung eosinophilia in mice following allergen challenge. However, both JAK inhibitors neither affected airway resistance nor compliance. CONCLUSION: Our data suggest that the JAK1/2 inhibitor baricitinib is even more potent than the JAK3 inhibitor tofacitinib in suppressing eosinophil effector function. Thus, targeting the JAK1/2 pathway represents a promising therapeutic strategy for eosinophilic inflammation as observed in severe eosinophilic asthma.


Assuntos
Azetidinas/uso terapêutico , Eosinofilia/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Animais , Azetidinas/farmacologia , Células Cultivadas , Eosinofilia/induzido quimicamente , Eosinofilia/imunologia , Eosinófilos/fisiologia , Feminino , Humanos , Janus Quinase 1/imunologia , Janus Quinase 2/imunologia , Inibidores de Janus Quinases/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Purinas/farmacologia , Pirazóis/farmacologia , Pyroglyphidae/imunologia , Sulfonamidas/farmacologia , Adulto Jovem
8.
Front Immunol ; 12: 687294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220841

RESUMO

Background: Several studies indicate that Der p 7 is an important and clinically relevant allergen of Dermatophagoides pteronyssinus which should be included in vaccines for treatment of house dust mite (HDM) allergy. Aim of this study was to characterize the IgE epitopes of Der p 7. Methods: Recombinant Der p 7 was expressed and purified, analyzed for fold by circular dichroism and tested for its allergenic activity by basophil activation. Seven overlapping, surface-exposed peptides (P1-P7) with a length of 27 to 37 amino acids, which spanned the Der p 7 sequence, were synthesized and tested for IgE reactivity and allergenic activity by basophil activation assay. Carrier-bound peptides were studied for their ability to induce allergen-specific IgG antibodies in rabbits. Peptide-specific antibodies were used to inhibit allergic patients` IgE binding to Der p 7 by ELISA for mapping of IgE epitopes. Results: rDer p 7 showed high allergenic activity comparable with Der p 5, Der p 21, and Der p 23. None of the seven tested peptides showed any IgE reactivity or allergenic activity when tested with HDM- allergic patients indicating lack of sequential IgE epitopes on Der p 7. IgE inhibition experiments using anti-peptide specific IgGs and molecular modeling enabled us to identify discontinuous, conformational IgE epitopes of Der p 7. Conclusion and Clinical Relevance: IgE epitopes of Der p 7 belong to the conformational and discontinuous type whereas sequential Der p 7 peptides lack IgE reactivity. It should thus be possible to construct hypoallergenic vaccines for Der p 7 based on carrier-bound allergen peptides.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Epitopos Imunodominantes , Imunoglobulina E/sangue , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/imunologia , Alérgenos/química , Alérgenos/genética , Animais , Antígenos de Dermatophagoides/química , Antígenos de Dermatophagoides/genética , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Mapeamento de Epitopos , Humanos , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Pyroglyphidae/genética , Coelhos , Ratos , Hipersensibilidade Respiratória/sangue
9.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067936

RESUMO

BACKGROUND AND AIM: Progress in laboratory diagnostics of IgE-mediated allergy is the use of component-resolved diagnosis. Our study analyses the results of specific IgE to 295 allergen reagents (117 allergenic extracts and 178 molecular components) in patients suffering from atopic dermatitis (AD) with the use of ALEX2 Allergy Explorer. METHOD: The complete dermatological and allergological examination, including the examination of the sensitization to molecular components with ALEX2 Allergy Explorer testing, was performed. The statistical analysis of results was performed with these methods: TURF (total unduplicated reach and frequency), best reach and frequency by group size, two-sided tests, Fisher's exact test, and chi-square test (at an expected minimum frequency of at least 5). RESULTS: Altogether, 100 atopic dermatitis patients were examined: 48 men, 52 women, the average age 40.9 years, min. age 14 years, max. age 67 years. The high and very high level of specific IgE was reached in 75.0% of patients to 18 molecular components: from PR-10 proteins (Aln g 1, Bet v 1, Cor a1.0103, Cor a1.0401, Fag s 1), lipocalin (Can f 1), NPC2 family (Der f 2, Der p 2), uteroglobin (Fel d 1), from Alternaria alternata (Alt a 1), Beta expansin (Lol p 1, Phl p 1), molecular components from Timothy, cultivated rye (Secc pollen) and peritrophin-like protein domain Der p 23. The high and very high level of specific IgE to other lipocalins (Fel d 7, Can f 4), to arginine kinase (Bla g 9, German cockroach), and to allergen extracts Art v (mugwort), and Cyn d (Bermuda grass) reached 52.0% of patients. The severity of AD is in significant relation to the sensitization to molecular components of storage mites (Gly d 2, Lep d 2-NPC2 family), lipocalins (Can f 1, Can f 2, Can f 4, and Can f 6), arginine kinase (Asp f 6, Bla g 9, Der p 20, Pen m 2), uteroglobin (Fel d 1, Ory c 3), Mn superoxide dismutase (Mala s 11), PR-10 proteins (Fag s 1, Mal d 1, Cor a 1.0401, Cor a 1.0103), molecular components of the peritrophin-like domain (Der p 21, Der p 23), and to Secc pollen. In the subgroup of patients suffering from bronchial asthma, the significant role play molecular components from house dust mites and storage mites (Lep d 2, Der p 2, Der f 2-NPC2 family), cysteine protease (Der p 1), peritrophin-like protein domain (Der p 21, Der p 23), enolase from Alternaria alternata (Alt a 6), and Beta expansin Phl p 1. CONCLUSION: The results of our study demonstrate the detailed profile of sensitization to allergens reagents (allergen extract and molecular components) in patients with atopic dermatitis. We show the significance of disturbed epidermal barrier, resulting in increased penetration of allergens. We confirmed the significant relationship between the severity of AD, the occurrence of bronchial asthma and allergic rhinitis, and high levels of specific IgE to allergen reagents. Our results may be important for regime measures and immunotherapy; Der p 23 shall be considered as an essential component for the diagnosis and specific immunotherapy of house dust mite allergy.


Assuntos
Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Imunoglobulina E/análise , Adolescente , Adulto , Idoso , Alérgenos , Animais , Asma/diagnóstico , Asma/imunologia , República Tcheca , Feminino , Humanos , Imunoglobulina E/metabolismo , Masculino , Pessoa de Meia-Idade , Pólen/imunologia , Pyroglyphidae/imunologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Testes Cutâneos/métodos
10.
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
11.
Ann Allergy Asthma Immunol ; 127(3): 312-317, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33971362

RESUMO

OBJECTIVE: To present an update of birth cohort study designs and their contributions to allergic risk. DATA SOURCES: The PubMed database was used to search for relevant articles. STUDY SELECTIONS: Peer-reviewed prospective and retrospective studies involving the assessment of allergy using human birth cohorts between 2014 and 2021 were evaluated. RESULTS: Parental history of allergic diseases, especially in cases involving both parents, is associated with increased risk of allergy. Exposure to prenatal and postnatal smoking and limited diet diversity were associated with increased allergic burden. The impact of early-life infections and antibiotics on disease development may be associated with the onset of asthma, though this remains debated. Cohort studies also revealed that the mode of delivery and breastfeeding duration affect the odds ratio of asthma and eczema development. Household exposures, including pets, house dust mites, and scented aeroallergens may confer protective effects, whereas high air pollution exposure and low socioeconomic status may be risk enhancing. Exposure to antibiotics during early life may be associated with increased asthma risk, whereas viral infections may lead to disease protection, though the impact of the coronavirus disease 2019 pandemic on allergic risk is yet to be understood. CONCLUSION: Although evaluating the risk of allergic disease development is complex, clinicians can apply these insights on the multifactorial nature of atopy to better understand and potentially mitigate disease development.


Assuntos
Asma/imunologia , Aleitamento Materno/métodos , Dieta/métodos , Eczema/imunologia , Hipersensibilidade/imunologia , Padrões de Herança/imunologia , Alérgenos/administração & dosagem , Animais , Antibacterianos/efeitos adversos , Asma/etiologia , Asma/genética , Asma/prevenção & controle , Estudos de Coortes , Eczema/etiologia , Eczema/genética , Eczema/prevenção & controle , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Feminino , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/genética , Hipersensibilidade/prevenção & controle , Animais de Estimação/imunologia , Gravidez , Pyroglyphidae/química , Pyroglyphidae/imunologia , Fatores de Risco , Viroses/imunologia , Viroses/virologia
12.
Int Arch Allergy Immunol ; 182(8): 690-696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34000723

RESUMO

INTRODUCTION: While there exists considerable evidence for efficacy of sublingual immunotherapy (SLIT), its impact on the improvement of nasal signs in allergic rhinitis (AR) patients remains quite unclear. In this study, the endoscopic examination and the modified Lund-Kennedy (MLK) scoring system were performed to describe and evaluate the therapeutic effect of SLIT. METHODS: A total of 105 patients with AR induced by house dust mites were enrolled and treated with standardized Dermatophagoides farinae (D. farinae) drops for 1 year. The total nasal symptoms score (TNSS), total medication score (TMS), visual analog scale (VAS), and MLK scores were assessed at baseline and 6 and 12 months. The MLK score was also compared for its correlation with TNSS, TMS, and VAS. RESULTS: The TNSS, TMS, and VAS scores statistically decreased after SLIT compared to baseline (all p < 0.05). After 12 months of treatment, the rates of well-controlled, partial controlled, and uncontrolled AR patients were 42, 49.5, and 8.5%, respectively. The nasal endoscopy findings showed significant improvement in nasal signs, which mainly included color change of turbinate mucosa, reduction of nasal secretions, and improvement of nasal edema. A significant decrease was observed in MLK scores, and there was a positive correlation between MLK and VAS scores. CONCLUSIONS: In addition to commonly utilized subjective assessments (TMS, TNSS, and VAS), our results of endoscopic examination and the MLK scores consistently confirmed that SLIT is an effective therapeutic modality for AR patients. The MLK scores might be considered as an auxiliary tool to evaluate efficacy of SLIT in clinical practice and outcomes research.


Assuntos
Alérgenos/imunologia , Endoscopia , Pyroglyphidae/imunologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/etiologia , Rinite Alérgica/terapia , Imunoterapia Sublingual , Animais , Antígenos de Dermatophagoides/imunologia , Tomada de Decisão Clínica , Gerenciamento Clínico , Endoscopia/métodos , Humanos , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/patologia , Índice de Gravidade de Doença , Imunoterapia Sublingual/métodos
13.
Int J Immunopathol Pharmacol ; 35: 20587384211015528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33985377

RESUMO

Sublingual immunotherapy (SLIT) has been used for more than three decades as a therapeutic strategy for the treatment of allergic diseases. Studies have demonstrated its efficacy and safety, and numerous clinical trials have evaluated these parameters. In the present study, through patient perception, we investigated the patient satisfaction with the use of house dust mite SLIT treatment. "Satisfaction Scale for Patients Receiving Allergen Immunotherapy" (ESPIA) questionnaire, a standardized and validated instrument for clinical studies evaluating allergen immunotherapy, was applied to allergic patients (N = 136). Children and adults of both sexes who received SLIT for Dermatophagoides pteronyssinus and/or Blomia tropicalis, according to the results of an immediate reading puncture test, were included. Data analysis showed that the perception of treatment effectiveness was 92%, performance improvement in the daily activities was 91%, a satisfactory cost-benefit balance was 84%, and the perception of general satisfaction was 97%. The results showed a high perception of satisfaction in allergic patients undergoing house dust mite SLIT.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Hipersensibilidade/terapia , Satisfação do Paciente , Imunoterapia Sublingual , Atividades Cotidianas , Adulto , Animais , Criança , Análise Custo-Benefício , Feminino , Humanos , Hipersensibilidade/economia , Masculino , Pyroglyphidae/imunologia , Testes Cutâneos , Imunoterapia Sublingual/economia , Inquéritos e Questionários , Resultado do Tratamento
14.
Ann Allergy Asthma Immunol ; 127(2): 165-175.e1, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029713

RESUMO

OBJECTIVE: Allergic rhinitis (AR) is an immunoglobulin (Ig) E-mediated inflammatory condition that causes sneezing, nasal congestion, rhinorrhea, and nasal itch. Although subcutaneous immunotherapy for the treatment of AR has been in use and well established as a treatment modality, sublingual immunotherapy (SLIT) is increasingly considered to be the safer and more convenient alternative. Thus, the objective of this review is to describe recent findings pertaining to the use of SLIT tablets (SLIT-T) for AR. DATA SOURCES: A database search (PubMed.gov) for articles published between January 1, 2017, and February 9, 2021, was conducted using the following key words: "allergic rhinitis," AND-ed "sublingual immunotherapy." Included were randomized placebo-controlled trials. Other experimental design studies were excluded. STUDY SELECTIONS: A total of 11 randomized placebo-controlled trials were selected for full-text review and included in the analysis. All studies investigated the use of SLIT on patients with seasonal AR (4 tree pollen, 1 grass pollen, and 1 Japanese cedar) or perennial AR (3 house dust mite). RESULTS: Our review of 7 recently published randomized placebo-controlled trials with 2348 subjects receiving SLIT reported increased efficacy, safety, supportive immunologic parameters (IgE and IgG4 pre- and posttreatment levels), and improved quality of life. All studies excluded subjects with overlapping seasonal or perennial allergens, a history of moderate-to-severe uncontrolled asthma, or reduced lung function. CONCLUSION: Our review highlights that SLIT is a safe and effective treatment that considerably reduces symptoms and medication requirements in AR and improves quality of life.


Assuntos
Alérgenos/administração & dosagem , Dessensibilização Imunológica/métodos , Pólen/imunologia , Rinite Alérgica/terapia , Imunoterapia Sublingual/efeitos adversos , Imunoterapia Sublingual/métodos , Adolescente , Adulto , Idoso , Alérgenos/imunologia , Ambrosia/imunologia , Animais , Antígenos de Plantas/imunologia , Criança , Pré-Escolar , Cryptomeria/imunologia , Humanos , Pessoa de Meia-Idade , Extratos Vegetais/imunologia , Poaceae/imunologia , Pyroglyphidae/imunologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
15.
Eur J Dermatol ; 31(2): 155-160, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33871374

RESUMO

BACKGROUND: Although specific IgE antibodies reactive to exogenous antigens are found in patients with atopic dermatitis (AD), some patients do not have such antibodies. Autoimmunity has been proposed as a possible mechanism in these patients. OBJECTIVES: To identify specific IgE antibodies reactive to human transglutaminase 3 (TG3) and tropomysin (TMP) and determine whether auto-reactive T cells are induced by these proteins in patients with AD. MATERIALS & METHODS: Forty-two patients with AD and 27 healthy controls were included in this study. IgE antibodies against recombinant human TG3 and TMP were measured by ELISA. Cross-reactivity between allergens was determined by EdU of peripheral blood mononuclear cells (PBMCs) proliferation assays. T-cell lines were generated from PBMCs in the presence of house dust mites (HDM), TG3 and TMP. TG3/TP-specific T-cell clones were generated from T-cell lines, and were characterized by antigen specificity and cytokine pattern. RESULTS: In 12 patients with anti-HDM IgE antibodies, six (50%) had anti-TG3 IgE antibody and four (33.3%) had both anti-TG3 and anti-TMP IgE antibodies. Lymphocyte proliferation was induced in 12 patients by TG3 or TMP. T-cell lines and T-cell clones from PBMCs of patients with AD who had IgE antibody reactive to HDM were fully cross-reactive with TG3 and TMP. These cell clones included both Th1 cell (producing IFN-γ) and Th2 cell (inducing IL-4) responses. TG3-and TMP-specific T-cell clones were not generated from healthy controls. CONCLUSION: Specific IgE antibody and T cell clones reactive to human TG3 and TMP were found in patients with AD, indicating that an autoimmune mechanism might contribute to AD.


Assuntos
Dermatite Atópica/imunologia , Imunoglobulina E/sangue , Pyroglyphidae/imunologia , Transglutaminases/imunologia , Tropomiosina/imunologia , Animais , Autoimunidade/imunologia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Reações Cruzadas/imunologia , Dermatite Atópica/sangue , Humanos , Interferon gama/metabolismo , Interleucina-4/metabolismo , Células Th1/imunologia , Células Th2/imunologia
16.
Ital J Pediatr ; 47(1): 101, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892756

RESUMO

BACKGROUND: Allergen immunotherapy (AIT) is the only causal therapy for IgE-mediated allergy. There is less evidence about the safety and efficacy of AIT especially subcutaneous immunotherapy (SCIT) in children under 5 years old. We aimed to investigate the side effects and associated risk factors of house dust mite (HDM) SCIT in preschool children with respiratory allergic diseases. METHODS: The preschool children who had HDM-related allergic rhinitis with/without asthma were enrolled and undergone standardized HDM SCIT in our department from June 2013 to December 2019. Local reactions (LRs) and systemic reactions (SRs) were recorded and categorized according to World Allergy Organization recommendations. Demographic data and other therapeutic-related parameters were also recorded to investigate potential risk factors for these side effects. RESULTS: A total of 91 children (60 boys, 65.93%; 31 girls, 34.07%; mean age 4.13 years old) were included in the study. Among the 91 patients, 3109 SCIT injections were recorded, 62/91 (68.13%) experienced 186 immediate LRs, 4 /91(4.40%) experienced 6 delayed LRs, 11/91 (12.09%) children experienced 44 immediate SRs, 21/44 (47.73%) were grade 1 SRs, 21/44 (47.73%) were grade 2, 2/44 (4.55%) were grade 3, no grade 4 or 5 SRs occurred. Furthermore, 1/91 (1.10%) experienced 1 delayed SRs, manifested by urticaria 2 days later after allergen injection. 9/91 (9.89%) experienced 2 or more times SRs. Multivariable logistic regression analysis showed BMI (OR 1.506; 95%CI 1.091 to 2.079; p < 0.05) and sIgE against HDM (OR 1.497; 95%CI 1.082 to 2.071; p < 0.05) were risk factors for LRs. No variable was found to correlate with SRs (all p > 0.05). CONCLUSIONS: HDM subcutaneous immunotherapy is considered to be safe in preschool children with respiratory allergic diseases. Higher BMI and HDM sIgE level in children are risk factors for developing LRs. The incidence of SRs and the rate of severe SRs are low in preschool children.


Assuntos
Asma/imunologia , Asma/terapia , Dessensibilização Imunológica/métodos , Pyroglyphidae/imunologia , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Animais , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/imunologia , Lactente , Masculino
17.
Acta Trop ; 220: 105934, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33895144

RESUMO

Allergic bronchial asthma is characterized by chronic inflammation of the respiratory airways mediated by T-helper 2 (Th2), Th17 and their cytokines. Although most asthmatic patients suffer from allergic airway remodeling (AAR), aggressive anti-allergic treatment failed to reverse it. The hygiene hypothesis illuminated the counter relationship between allergy and helminthic infections. The immune system is modulated by Trichinella spiralis (T. spiralis) infection to maintain homeostasis. Therefore, this work aimed to investigate the impact of chronic T. spiralis infection on induced AAR in C57BL/6 mice sensitized by house dust mites (HDM) allergens. Forty mice were divided into 3 groups: I (10 healthy mice), IΙ (15 HDM sensitized mice), and ΙΙI (15 T. spiralis chronically infected mice and sensitized with HDM allergens). The assessment aimed to evaluate the effects of regulatory CD4+CD25+FOXP3+ cells (Tregs) and their cytokines comparative to hypersensitivity mediated cytokines. Chronic T. spiralis infection effectively prevented the host's AAR. This result was evidenced by upregulated Tregs in blood by flow cytometric analysis and increased interleukin-10 (IL-10) levels in bronchoalveolar lavage (BAL) by Enzyme linked immunosorbent assay (ELISA) as well as improved lung histopathological changes. Also, serum HDM specific immunoglobulin E (IgE), BAL eosinophils, BAL IL-5 levels, and IL-17 gene expression in lung tissues were significantly reduced in T. spiralis chronically infected mice. In conclusion, the immune response in chronic T. spiralis infection could provide a promising mechanistic tool for protection against AAR, which paves the way for innovative preventive measures of other immunological disorders.


Assuntos
Remodelação das Vias Aéreas/imunologia , Pyroglyphidae/imunologia , Triquinelose/imunologia , Alérgenos/imunologia , Alérgenos/farmacologia , Animais , Asma/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Humanos , Imunoglobulina E/sangue , Inflamação/imunologia , Interleucinas/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/imunologia , Trichinella spiralis
18.
Inflamm Res ; 70(5): 569-579, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33852061

RESUMO

BACKGROUND: Asthma is one of the most common noninfectious chronic diseases characterized by type II inflammation. This study aimed to investigate the effects of molecular hydrogen on the pathogenesis of asthma. METHODS: OVA sensitized asthma mouse model and house dust mite treated 16HBE cellular model were established and hydrogen/oxygen mixture was used to treat asthmatic mice and 16HBE cells. Serum and BALF cytokines were measured with specific ELISA assays. E-cadherin and ZO-1 were detected by immunohistochemical staining and expression of caspase 3 and 9, NF-κB, IL-33 and ST2 was assessed by quantitative real-time PCR, western blot and/or immunofluorescence. IL-33 promoter activity was analyzed by dual-luciferase assay. ILC2 population was assayed by flow cytometry and differentially expressed miRNAs were detected using miRNA array. RESULTS: Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H2 in asthmatic mice. The expression of NF-κB (p65) and ST2 was upregulated by OVA and suppressed by H2. ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H2. E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H2 treatment. H2 alleviated HDM induced apoptosis of 16HBE cells, upregulation of IL-33 and ST2, and elevation of IL-33 promoter activity. A group of miRNAs differentially expressed in HDM and HDM + H2 treated 16HBE cells were identified. CONCLUSIONS: These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutics for asthma and other conditions of type II inflammation.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Citocinas/imunologia , Hidrogênio/uso terapêutico , Alérgenos/imunologia , Animais , Antiasmáticos/farmacologia , Apoptose/efeitos dos fármacos , Asma/sangue , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Linhagem Celular , Citocinas/sangue , Citocinas/genética , Células Epiteliais/imunologia , Feminino , Humanos , Hidrogênio/farmacologia , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Camundongos Endogâmicos ICR , MicroRNAs/genética , Ovalbumina/imunologia , Pyroglyphidae/imunologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia
19.
PLoS Pathog ; 17(3): e1009337, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33651853

RESUMO

The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation.


Assuntos
Poeira/imunologia , Hipersensibilidade/imunologia , Pyroglyphidae/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Proteínas de Helminto/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Camundongos , Proteômica
20.
Int Arch Allergy Immunol ; 182(7): 563-570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730726

RESUMO

INTRODUCTION: Environmental exposure to mites and fungi has been proposed to critically contribute to the development of IgE-mediated asthma. A common denominator of such organisms is chitin. Human chitinases have been reported to be upregulated by interleukin-13 secreted in the context of Th2-type immune responses and to induce asthma. We assessed whether chitin-containing components induced chitinases in an innate immune-dependent way and whether this results in bronchial hyperresponsiveness. MATERIALS AND METHODS: Monocyte/macrophage cell lines were stimulated with chitin-containing or bacterial components in vitro. Chitinase activity in the supernatant and the expression of the chitotriosidase gene were measured by enzyme assay and quantitative PCR, respectively. Non-sensitized mice were stimulated with chitin-containing components intranasally, and a chitinase inhibitor was administered intraperitoneally. As markers for inflammation leukocytes were counted in the bronchoalveolar lavage (BAL) fluid, and airway hyperresponsiveness was assessed via methacholine challenge. RESULTS: We found both whole chitin-containing dust mites as well as the fungal cell wall component zymosan A but not endotoxin-induced chitinase activity and chitotriosidase gene expression in vitro. The intranasal application of zymosan A into mice led to the induction of chitinase activity in the BAL fluid and to bronchial hyperresponsiveness, which could be reduced by applying the chitinase inhibitor allosamidin. DISCUSSION: We propose that environmental exposure to mites and fungi leads to the induction of chitinase, which in turn favors the development of bronchial hyperreactivity in an IgE-independent manner.


Assuntos
Alérgenos/imunologia , Asma/diagnóstico , Asma/etiologia , Quitinases/efeitos adversos , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/etiologia , Animais , Antígenos de Fungos/imunologia , Biomarcadores , Linhagem Celular , Modelos Animais de Doenças , Feminino , Lectinas Tipo C , Camundongos , Pyroglyphidae/imunologia , Receptor 2 Toll-Like/metabolismo
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