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1.
Sci Rep ; 13(1): 144, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599893

RESUMO

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with complex environmental and genetic predisposing factors. Primary skin barrier dysfunction and aberrant T helper 2 (TH2) responses to common allergens, together with increased serum IgE antibodies, characterise the disease. B and T cells are essential in the disease manifestation, however, the exact mechanism of how these cells is involved is unclear. Targeting interleukin 4 receptor alpha (IL-4Rα), an IL-4/IL-13 signalling axis, with dupilumab shows efficacy in AD. We investigated the importance of IL-4Rα signalling specifically on B and T cells during acute and chronic models of AD. We used House dust mite (HDM) and Ovalbumin (OVA) in chronic models and a low-calcemic analog of vitamin D (MC903) for acute models of AD. We used mb1creIL-4Rα-/lox, iLCKcreIL-4Rα-/lox, LCKcreIL-4Rα-/lox, CD4creIL-4Rα-/lox, Foxp3creIL-4Rα-/lox and IL-4Rα-/lox littermate controls. IL-4Rα-responsive B cells were essential in serum IgE levels, but not in epidermal thickening in both chronic and acute models. IL-4Rα-responsive T cells were essential in epidermal thickening in the pan-T cell, but not CD4 or CD8 T cells suggesting the importance of γδT cells during acute AD. Our results suggest that IL-4Rα responsiveness on innate T cells regulates acute atopic dermatitis, while on B cells it regulates IgE.


Assuntos
Linfócitos B , Dermatite Atópica , Subunidade alfa de Receptor de Interleucina-4 , Células Th2 , Animais , Camundongos , Alérgenos/efeitos adversos , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Imunoglobulina E/sangue , Imunoglobulina E/química , Camundongos Endogâmicos BALB C , Camundongos Knockout , Células Th2/metabolismo , Células Th2/patologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Receptores de Interleucina-4/metabolismo , Subunidade alfa de Receptor de Interleucina-4/metabolismo
2.
Wien Klin Wochenschr ; 134(21-22): 766-771, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36074179

RESUMO

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but it may also appear in allergic rhinitis. The type of allergen, as well as regional characteristics, play an important role in the development of BHR. The aim of our study was to analyze allergen sensitization patterns and the factors that affect BHR in allergic rhinitis patients living in temperate continental climate zone. METHODS: This study retrospectively analyzed allergic rhinitis patients from Eastern Slovakia who underwent skin-prick tests to aeroallergens, spirometry, histamine and methacholine bronchial provocation tests for evaluation of lower airway symptoms. We analyzed the associations between BHR and the pattern of aeroallergen sensitization, lung function parameters, and the total IgE and eosinophil levels. RESULTS: Out of 365 allergic rhinitis patients (age range 16-64 years), 114 showed BHR. Sensitization to house dust mites (HDMs) and grass were the most common. BHR was significantly associated with sensitization to dogs (odds ratio, OR = 2.15, 95% confidence interval, CI: 1.13-4.11) and Alternaria (OR = 2.15, 95% CI: 1.06-4.35); however, BHR did not show a relationship with HDMs sensitization. The levels of total IgE and eosinophils were higher in the BHR-positive group. Sensitization to more than six allergens significantly increased the probability of BHR (p < 0.01). CONCLUSION: Dogs and Alternaria, but not HDMs, were the sensitizing agents most closely associated with BHR. High-grade sensitization and increased total IgE and eosinophil levels were characteristic clinical signs in BHR-positive allergic rhinitis patients in the temperate continental climatic zone.


Assuntos
Hiper-Reatividade Brônquica , Rinite Alérgica , Animais , Cães , Alérgenos , Hiper-Reatividade Brônquica/sangue , Hiper-Reatividade Brônquica/diagnóstico , Imunoglobulina E/sangue , Estudos Retrospectivos , Rinite Alérgica/epidemiologia , Biomarcadores/sangue , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Clima
3.
Front Immunol ; 13: 902652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928809

RESUMO

Background: The pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSUaiTIIb) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that an enhanced signal transducer and activator of transcription 3 (STAT3) may be responsible for reduced IgE serum levels. Objective: Our aim was to investigate a possible underlying gain-of-function mutation or activating polymorphism in STAT3 that could be responsible for the low levels of IgE in patients with CSUaiTIIb. Methods: We included 10 patients with CSUaiTIIb and low levels of IgE and sequenced selected single nucleotide polymorphisms (SNP) in STAT3 associated with common autoimmune diseases. Exon sequencing was performed for the most relevant exons of STAT3. To test for a gain-of-function of STAT3, we performed a phospho-specific flow cytometry analysis of STAT3 in peripheral blood mononuclear cells before and after stimulation with interleukin-6. Results: No differences were found in the prevalence of the tested SNPs between our patients and a control population. Moreover, we could not find any mutations or variants on the tested exons of STAT3. The function of STAT3 was also not altered in our patients. Conclusion: In total, we could not find any evidence for our hypothesis that low IgE in patients with CSUaiTIIb is linked to mutations in STAT3 or altered activity of STAT3. Thus, it remains to be discovered what causes the low serum levels of IgE in patients with CSUaiTIIb.


Assuntos
Urticária Crônica , Imunoglobulina E , Fator de Transcrição STAT3 , Urticária Crônica/sangue , Urticária Crônica/genética , Mutação com Ganho de Função , Humanos , Imunoglobulina E/sangue , Leucócitos Mononucleares , Fator de Transcrição STAT3/sangue , Fator de Transcrição STAT3/genética
4.
Allergol Int ; 71(4): 512-519, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35718709

RESUMO

BACKGROUND: The mechanism of allergic reactions to COVID-19 mRNA vaccines has not been clarified. Polyethylene glycol (PEG) is a potential antigen in the components of vaccines. However, there is little evidence that allergy after COVID-19 mRNA vaccination is related to PEG. Furthermore, the role of polysorbate (PS) as an antigen has also not been clarified. The objective of this study was to investigate whether PEG and PS allergies are reasonable causes of allergic symptoms after vaccination by detecting PEG-specific and PS-specific antibodies. METHODS: Fourteen patients who developed immediate allergic reactions to BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines and nineteen healthy controls who did not present allergic symptoms were recruited. Serum PEG-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) and PS-specific IgE and IgG were measured by enzyme-linked immunosorbent assay. Skin tests using PEG-2000 and PS-80 were applied to five patients and three controls. RESULTS: Serum levels of PEG-specific IgE and IgG in patients with immediate allergic reactions to the COVID-19 mRNA vaccine were higher than those in the control group. Serum levels of PS-specific IgE in patients with allergy to the vaccine were higher than those in patients of the control group. Intradermal tests using PEG verified the results for PEG-specific IgE and IgG. CONCLUSIONS: The results suggest that PEG is one of the antigens in the allergy to COVID-19 mRNA vaccines. Cross-reactivity between PEG and PS might be crucial for allergy to the vaccines. PEG-specific IgE and IgG may be useful in diagnosing allergy to COVID-19 mRNA vaccines.


Assuntos
Vacina BNT162/efeitos adversos , COVID-19 , Hipersensibilidade , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade Imediata , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Polietilenoglicóis , Polissorbatos , RNA Mensageiro , Vacinas Sintéticas , Vacinas de mRNA
5.
mBio ; 13(3): e0374221, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35475643

RESUMO

Lymphatic filariasis is a debilitating disease that afflicts over 70 million people worldwide. It is caused by the parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Despite substantial success, efforts to eliminate LF will likely require more time and resources than predicted. Identifying new drug and vaccine targets in adult filariae could help elimination efforts. This study's aim was to evaluate intestinal proteins in adult Brugia malayi worms as possible therapeutic targets. Using short interfering RNA (siRNA), we successfully targeted four candidate gene transcripts: Bma-Serpin, Bma-ShTK, Bma-Reprolysin, and Bma-LAD-2. Of those, Bma-LAD-2, an immunoglobulin superfamily cell adhesion molecule (IgSF CAM), was determined to be essential for adult worm survival. We observed a 70.42% knockdown in Bma-LAD-2 transcript levels 1 day post-siRNA incubation and an 87.02% reduction in protein expression 2 days post-siRNA incubation. This inhibition of Bma-LAD-2 expression resulted in an 80% decrease in worm motility over 6 days, a 93.43% reduction in microfilaria release (Mf) by day 6 post-siRNA incubation, and a dramatic decrease in (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Transmission electron microscopy revealed the loss of microvilli and unraveling of mitochondrial cristae in the intestinal epithelium of Bma-LAD-2 siRNA-treated worms. Strikingly, Bma-LAD-2 siRNA-treated worms exhibited an almost complete loss of pseudocoelomic fluid. A luciferase immunoprecipitation system assay did not detect anti-Bma-LAD-2 IgE in the serum of 30 LF patients, indicating that LF exposure does not result in IgE sensitization to this antigen. These results indicate that Bma-LAD-2 is an essential protein for adult Brugia malayi and may be an effective therapeutic target. IMPORTANCE Brugia malayi is a parasitic nematode that can cause lymphatic filariasis, a debilitating disease prevalent in tropical and subtropical countries. Significant progress has been made toward eliminating the disease. However, complete eradication may require new therapeutics such as drugs or a vaccine that kill adult filariae. In this study, we identified an immunoglobulin superfamily cell adhesion molecule (Bma-LAD-2) as a potential drug and vaccine candidate. When we knocked down Bma-LAD-2 expression, we observed a decrease in worm motility, fecundity, and metabolism. We also visualized the loss of microvilli, destruction of the mitochondria in the intestinal epithelium, and loss of pseudocoelomic fluid contents after Bma-LAD-2 siRNA treatment. Finally, we demonstrated that serum from filaria-infected patients does not contain preexisting IgE to Bma-LAD-2, which indicates that this antigen would be safe to administer as a vaccine in populations where the disease is endemic.


Assuntos
Brugia Malayi , Moléculas de Adesão Celular , Filariose Linfática , Proteínas de Helminto , Animais , Brugia Malayi/genética , Adesão Celular , Moléculas de Adesão Celular/genética , Filariose Linfática/tratamento farmacológico , Proteínas de Helminto/genética , Humanos , Imunoglobulina E/sangue , RNA Interferente Pequeno/genética
6.
Dis Markers ; 2022: 5651506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35256891

RESUMO

IgG4-related disease (IgG4-RD) affects multiple organs and is characterized by immune-mediated inflammation and fibrosis; IgG-RD affecting orbital tissue is known as IgG4-related ophthalmic disease (IgG4-ROD). This research is aimed at exploring whether symptom duration and common serologic factors, such as IgG, IgE, and eosinophils, are potential risk factors for IgG4-ROD patient relapse after surgery and identifying possible causes of the positive correlation between symptom duration and relapse. This retrospective cohort study included 40 IgG4-ROD patients after surgery. Auxiliary inspection results were obtained before surgery and during follow-up, and relapse risk factors were identified based on previous studies. We used the Spearman rank correlation test to reveal the relationship between symptom duration and relapse time and identified the optimal cutoff value for symptom duration by X-tile. Then, we divided the patients into the long-duration and short-duration groups. Kaplan-Meier survival analyses and log-rank tests were performed to identify the relationship between symptom duration and relapse using X-tile software. Finally, we studied the relationship between previously studied relapse risk factors and symptom duration. The survival curves of the long-duration and short-duration groups were obviously different, and the baseline serum IgG, IgE, and eosinophil levels and asthma concomitant rate were significantly different between the long-duration and short-duration groups. Furthermore, the baseline serum IgG (r = 0.485, P = 0.002), IgE (r = 0.350, P = 0.037), and eosinophil (r = 0.6535, P < 0.0001) levels were positively correlated with symptom duration. Our study shows that IgG4-ROD symptom duration is significantly positively correlated with relapse rate and negatively correlated with relapse time. Symptom duration was positively correlated with serum baseline IgG4, IgE, and eosinophil levels and asthma history, which were potential risk factors for disease relapse. We recommended that IgG4-ROD patients with symptom durations greater than 96 months continue to receive maintenance steroid therapy longer than 1 year postsurgery to reduce the relapse rate.


Assuntos
Eosinófilos/metabolismo , Oftalmopatias/cirurgia , Imunoglobulina E/sangue , Doença Relacionada a Imunoglobulina G4/cirurgia , Imunoglobulina G/sangue , Adulto , Idoso , Biomarcadores/sangue , Oftalmopatias/sangue , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia , Feminino , Seguimentos , Humanos , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/imunologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
7.
Molecules ; 27(4)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35209002

RESUMO

Wheat allergens are responsible for symptoms in 60-70% of bakers with work-related allergy, and knowledge, at the molecular level, of this disorder is progressively accumulating. The aim of the present study is to investigate the panel of wheat IgE positivity in allergic Italian bakers, evaluating a possible contribution of novel wheat allergens included in the water/salt soluble fraction. The water/salt-soluble wheat flour proteins from the Italian wheat cultivar Bolero were separated by using 1-DE and 2-DE gel electrophoresis. IgE-binding proteins were detected using the pooled sera of 26 wheat allergic bakers by immunoblotting and directly recognized in Coomassie stained gel. After a preparative electrophoretic step, two enriched fractions were furtherly separated in 2-DE allowing for detection, by Coomassie, of three different proteins in the range of 21-27 kDa that were recognized by the pooled baker's IgE. Recovered spots were analyzed by nanoHPLC Chip tandem mass spectrometry (MS/MS). The immunodetected spots in 2D were subjected to mass spectrometry (MS) analysis identifying two new allergenic proteins: a glucose/ribitol dehydrogenase and a 16.9 kDa class I heat shock protein 1. Mass spectrometer testing of flour proteins of the wheat cultivars utilized by allergic bakers improves the identification of until now unknown occupational wheat allergens.


Assuntos
Alérgenos/imunologia , Glucose 1-Desidrogenase/imunologia , Proteínas de Choque Térmico Pequenas/imunologia , Proteínas de Plantas/imunologia , Desidrogenase do Álcool de Açúcar/imunologia , Hipersensibilidade a Trigo/imunologia , Adulto , Idoso , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Testes de Função Respiratória , Testes Cutâneos , Espectrometria de Massas em Tandem , Hipersensibilidade a Trigo/diagnóstico
9.
Sci Rep ; 12(1): 2884, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35190607

RESUMO

Prenatal oxidative balance might influence cord blood IgE (cIgE) levels. We aimed to explore if certain prenatal dietary sources of antioxidants and pro-oxidants are associated with cIgE elevation and if they interact with IL4 and IL13 pathway genes. A structured questionnaire was completed during the third trimester of pregnancy for 1107 full-term newborns. Surveyed antioxidant-enriched food included fish, shellfish, and fruit, whereas surveyed pro-oxidant-contained food included fried fish sticks and canned fish. Cord blood was collected for measuring cIgE levels and genotyping IL13 rs1800925, rs20541, rs848, IL4 rs2243250, and STAT6 rs324011. Fairly lean fish consumption showed protection against cIgE elevation (odds ratio [OR] 0.66; 95% CI 0.49-0.90) in the whole sample, while daily fruit (OR 0.46; 95% CI 0.27-0.79) and ≥ monthly canned fish (OR 2.81; 95% CI 1.24-6.36) exhibited associations only in genetically susceptible babies. A prenatal food protective index, comprising any fairly lean fish, daily fruit, and the absence of any canned fish, exerted dose-response protection against cIgE elevation in babies carrying the IL13 rs20541 GA or AA genotype (P for trend < 0.0001; P for interaction = 0.004). We concluded that prenatal antioxidant-enriched and pro-oxidant-contained food consumption may influence cIgE, especially in genetically susceptible babies.


Assuntos
Antioxidantes/administração & dosagem , Dieta , Ingestão de Alimentos/fisiologia , Sangue Fetal/metabolismo , Análise de Alimentos , Imunoglobulina E/sangue , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Troca Materno-Fetal/fisiologia , Efeitos Tardios da Exposição Pré-Natal/sangue , Espécies Reativas de Oxigênio/administração & dosagem , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Inquéritos e Questionários
10.
Mol Immunol ; 143: 50-57, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35038659

RESUMO

Asthma is a disease with complicated network of inflammatory responses of cytokines and ImmunoglobulinE (IgE). The aim of this study was to explore the clinical characteristics, cytokine profile and plasma IgE in the Malaysian population. This is a cross-sectional study involving physician-diagnosed asthma patients (n = 287) recruited from the Chest Clinic, University of Malaya Medical Centre (UMMC). Blood (8 mL) was taken after consent was obtained. The peripheral blood leucocytes (PBL) were cultured in presence of a mitogen for 72 h to quantify cytokines [Interleukin-5(IL-5), Interleukin-9 (IL-9), Interleukin-12 Beta (IL-12ꞵ) and granulocyte-macrophage colony-stimulating factor (GM-CSF)] and plasma was used to quantify IgE levels with commercial ELISA kits. Results were compared against the same biomarkers in healthy subjects (n = 203). In addition, the amount of the biomarkers in the asthma patients were compared with their disease severity and clinical characteristics. Statistical tests in the SPSS software (Mann-Whitney U test and the Kruskal Wallis) were used to compare cytokine production and plasma IgE levels. The mean plasma IgE level was markedly higher (p < 0.0001) in asthmatics compared to controls. There were higher levels of IL-5, IL-9, IL-12ꞵ and GM-CSF (p < 0.0001) produced by cultured PBL from asthma patients compared to controls. However, our results did not expose a significant association between these cytokine levels and severity and clinical symptoms of asthma. However, there was a marked association between asthma severity and blood lymphocyte count [ꭓ2(2) = 6.745, p < 0.05]. These findings support the roles played by cytokines and IgE in the airway inflammation in asthma. The findings of this study provide new information about inflammatory cytokines in Malaysian asthma patients.


Assuntos
Asma/sangue , Asma/imunologia , Citocinas/sangue , Imunoglobulina E/sangue , Adolescente , Adulto , Idoso , Asma/patologia , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
11.
Comput Math Methods Med ; 2022: 1452116, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35047052

RESUMO

OBJECTIVES: This study sought to examine whether ligustrazine was capable of inhibiting phosphodiesterase (PDE) activity and improving lung function in a rat model of asthma. METHODS: Rats were initially sensitized using ovalbumin (OVA) and then were challenged daily with aerosolized OVA beginning 14 days later (30 min/day) to generate a rat model of asthma. Changes in airway function following methacholine (MCh) injection were evaluated by monitoring lung resistance (R L) and dynamic lung compliance (C dyn) values using an AniRes2005 analytic system. In addition, serum IgE was measured via ELISA, while PDE expression was evaluated via qPCR and western blotting. Key Findings. Ligustrazine significantly impaired allergen-induced lung hyperresponsivity and inflammation in this asthma model system. Ligustrazine treatment was also associated with reduced expression of PDEs including PDE4 in the lungs of these rats. CONCLUSIONS: Ligustrazine suppresses airway inflammation and bronchial hyperresponsivity in this rat model system, and these changes are associated with decreased PDE expression at the protein and mRNA levels.


Assuntos
Asma/tratamento farmacológico , Inibidores de Fosfodiesterase/farmacologia , Pirazinas/farmacologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Alérgenos/administração & dosagem , Alérgenos/imunologia , Animais , Asma/imunologia , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Biologia Computacional , Modelos Animais de Doenças , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Diester Fosfórico Hidrolases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/fisiopatologia
12.
Nutrients ; 14(2)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35057567

RESUMO

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobin E-mediated food hypersensitivity disorder. However, little is known about the clinical features of FPIES in patients with Down syndrome (DS). Medical records of children with DS diagnosed at our hospital between 2000 and 2019 were retrospectively reviewed. Among the 43 children with DS, five (11.6%) were diagnosed with FPIES; all cases were severe. In the FPIES group, the median age at onset and tolerance was 84 days and 37.5 months, respectively. Causative foods were cow's milk formula and wheat. The surgical history of colostomy was significantly higher in the FPIES group than in the non-FPIES group. A colostomy was performed in two children in the FPIES group, both of whom had the most severe symptoms of FPIES, including severe dehydration and metabolic acidosis. The surgical history of colostomy and postoperative nutrition of formula milk feeding may have led to the onset of FPIES. Therefore, an amino acid-based formula should be considered for children who undergo gastrointestinal surgeries, especially colostomy in neonates or early infants. When an acute gastrointestinal disease is suspected in children with DS, FPIES should be considered. This may prevent unnecessary tests and invasive treatments.


Assuntos
Síndrome de Down/imunologia , Enterocolite/imunologia , Hipersensibilidade Alimentar/imunologia , Alérgenos/imunologia , Animais , Estudos de Casos e Controles , Bovinos , Pré-Escolar , Colostomia/efeitos adversos , Proteínas na Dieta/imunologia , Enterocolite/diagnóstico , Enterocolite/epidemiologia , Humanos , Imunoglobulina E/sangue , Lactente , Fórmulas Infantis/efeitos adversos , Leite/imunologia , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Síndrome , Hipersensibilidade a Trigo/imunologia
13.
Arterioscler Thromb Vasc Biol ; 42(3): 352-361, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35045730

RESUMO

BACKGROUND: Treating known risk factors for coronary artery disease (CAD) has substantially reduced CAD morbidity and mortality. However, a significant burden of CAD remains unexplained. Immunoglobulin E sensitization to mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal) was recently associated with CAD in a small observational study. We sought to confirm that α-Gal sensitization is associated with CAD burden, in particular noncalcified plaque. Additionally, we sort to assess whether that α-Gal sensitization is associated with ST-segment-elevated myocardial infarction (STEMI) Methods: We performed a cross-sectional analysis of participants enrolled in the BioHEART cohort study. We measured α-Gal specific-immunoglobulin E antibodies in serum of 1056 patients referred for CT coronary angiography for suspected CAD and 100 selected patients presenting with STEMI, enriched for patients without standard modifiable risk factors. CT coronary angiograms were assessed using coronary artery calcium scores and segmental plaque scores. RESULTS: α-Gal sensitization was associated with presence of noncalcified plaque (odds ratio, 1.62 [95% CI, 1.04-2.53], P=0.03) and obstructive CAD (odds ratio, 2.05 [95% CI, 1.29-3.25], P=0.002), independent of age, sex, and traditional risk factors. The α-Gal sensitization rate was 12.8-fold higher in patients with STEMI compared with matched healthy controls and 2.2-fold higher in the patients with STEMI compared with matched stable CAD patients (17% versus 1.3%, P=0.01 and 20% versus 9%, P=0.03, respectively). CONCLUSIONS: α-Gal sensitization is independently associated with noncalcified plaque burden and obstructive CAD and occurs at higher frequency in patients with STEMI than those with stable or no CAD. These findings may have implications for individuals exposed to ticks, as well as public health policy. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001322224.


Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/imunologia , Hipersensibilidade Alimentar/complicações , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Idoso , Animais , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Dissacarídeos/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Calcificação Vascular/diagnóstico por imagem
14.
Cell Mol Life Sci ; 79(2): 87, 2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35067747

RESUMO

Aminoacyl-tRNA synthetases (ARSs) are emerging as important regulators in various immune diseases; however, their roles in immune cells remain unclear. In this study, using alanyl-tRNA synthetase (AARS) mutant (sti) mice with neurodegenerative disorder, we investigated the effect of translational fidelity in immune cells. Dysfunctional AARS caused disorders in immune cell responses and cellularity. The impairment was caused by dampened TCR signaling than cytokine signaling. Therefore, sti mutant inhibits TCR signaling, impeding T cell survival and responses. B cell numbers were decreased in sti mice. Despite low B cell cellularity, serum IgM, IgA, and IgE levels were higher in sti mice than in wild-type mice. Misacylation of ARS and the consequent translational infidelity induce disturbances in signaling pathways critical for immune cell survival and responses. Our findings provide a novel mechanism by which translational fidelity might play a critical role in cellular and humoral immune responses.


Assuntos
Aminoacil-tRNA Sintetases/genética , Linfócitos B/imunologia , Linfócitos T/imunologia , Aminoacil-tRNA Sintetases/metabolismo , Animais , Linfócitos B/citologia , Linfócitos B/metabolismo , Proliferação de Células/efeitos dos fármacos , Citocinas/farmacologia , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina M/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutagênese , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/citologia , Linfócitos T/metabolismo
15.
J Ethnopharmacol ; 289: 115023, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35074454

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis constitutes a traditional Korean medicine used for the treatment of atopic dermatitis, and honokiol is an active diphenyl compound present in Magnolia officinalis. AIM OF THE STUDY: The aim of the study was to investigate the therapeutic effects of honokiol on atopic dermatitis in vivo. MATERIALS AND METHODS: The therapeutic effects of honokiol were evaluated in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis model. RESULTS: Administration of honokiol (10 mg/kg) significantly suppressed mast cell accumulation and inflammation induced by DNCB in skin tissues. Moreover, DNCB-induced increases in serum immunoglobulin E levels were reversed by honokiol treatment. In addition, DNCB-induced elevation of inflammatory cytokines (interleukin (IL)-4, IL-13, IL-17, and interferon-γ) in the skin and lymph nodes was significantly ameliorated by honokiol administration. Furthermore, the increase in lymph nodes sizes induced by DNCB treatment was reduced by honokiol administration. CONCLUSION: DNCB-induced atopic responses in the ears and lymph nodes were significantly suppressed by honokiol treatment. These results suggested that honokiol is a potential therapeutic agent for atopic dermatitis.


Assuntos
Compostos de Bifenilo/farmacologia , Dermatite Atópica/tratamento farmacológico , Lignanas/farmacologia , Magnolia/química , Animais , Compostos de Bifenilo/isolamento & purificação , Citocinas/metabolismo , Dermatite Atópica/patologia , Dinitroclorobenzeno , Imunoglobulina E/sangue , Inflamação/tratamento farmacológico , Inflamação/patologia , Lignanas/isolamento & purificação , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C
16.
Int Immunopharmacol ; 104: 108509, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34998035

RESUMO

The present study aims to investigate the effects of CCR3 gene knockout in bone marrow cells (CCR3-KO) on the mouse model of combined allergic rhinitis and asthma syndrome (CARAS). It was found that CCR3-KO significantly reduced eosinophil (EOS) migration into the nasal (NALF) and bronchoalveolar (BALF) cavities of mice, and decreased Th2 cytokines (such as, IL-4, IL-5 and IL-13) levels in nasal mucosa and lung tissues. In addition, histological analysis showed that the damage degree of nasal mucosa structure in ovalbumin (OVA) modulated CCR3-KO mice was significantly less than that in OVA modulated Wild type (WT) mice, with reduced inflammatory cell infiltration and nasal mucus secretion. The infiltration of inflammatory cells in lung tissue was significantly reduced, and the proliferation of lung smooth muscle layer and extracellular matrix (ECM) production were decreased. Symptom analysis showed that CCR3-KO can reduced allergic rhinitis (AR) signals as nose scratching and sneezing. It was also found CCR3-KO reduce OVA-induced weight loss. The results showed that CCR3-KO could reduce the symptoms of allergic inflammation in CARAS mice by reducing airway inflammatory cell infiltration and down-regulating the expression of Th2 cytokines, and CCR3 gene could be used as a target gene for the treatment of CARAS.


Assuntos
Asma/genética , Receptores CCR3/genética , Rinite Alérgica/genética , Alérgenos/imunologia , Animais , Asma/metabolismo , Asma/patologia , Células da Medula Óssea , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/genética , Eosinófilos/imunologia , Imunoglobulina E/sangue , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Líquido da Lavagem Nasal/citologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Ovalbumina/imunologia , Receptores CCR3/metabolismo , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Síndrome , Células Th2
17.
J Clin Lab Anal ; 36(2): e24222, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34994992

RESUMO

INTRODUCTION: Multiple allergen simultaneous test (MAST) is widely used as a screening tool for allergic diseases and has the advantage of providing specific IgE (sIgE) results for various allergens in semiquantitative class. We have continuously conducted external quality assessment (EQA) since 2012 for clinical laboratories performing MAST using AdvanSure allergy screen test (LG CHEM, Korea). This study provides an account of the EQA experience. METHODS: Samples were prepared using pooled sera collected from patients with suspected allergic disease and sent to each laboratory twice a year. Each round included 4-6 serum samples with sIgE for 10-20 inhaled or food allergens. The acceptable class value was the most frequently reported MAST class ±1 titer that exceeded 80% of the total laboratory results. RESULTS: The average number of participating laboratories was 76 (49-90) and the average response rate was 97.3% during the entire survey period. The acceptable rates were consistently high at 97.7% ± 3.7%. Of the total 537 trials, 18 trials (3.4%) were regarded as nonconsensus results, in which acceptable answers did not exceed 80%. For unacceptable results, the false-negative rate (1.5% ± 2.8%) was higher than the false-positive rate (0.8% ± 2.7%) (p < 0.001). MAST class results were correlated with quantitative IgE results by ImmunoCAP (Spearman's correlation coefficient of 0.682 (p < 0.001) and gamma index of 0.777 (p < 0.001). CONCLUSION: Although EQA for MAST showed a high level of acceptable answer, some allergen assays require harmonization. Continuous performance of systematic EQA is needed to improve the accuracy of sIgE assays and quality control in clinical laboratories.


Assuntos
Alérgenos/sangue , Hipersensibilidade/diagnóstico , Imunoglobulina E/sangue , Garantia da Qualidade dos Cuidados de Saúde , Técnicas de Laboratório Clínico , Erros de Diagnóstico/estatística & dados numéricos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Humanos , Hipersensibilidade/imunologia , Medições Luminescentes , República da Coreia
18.
Respir Res ; 23(1): 1, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983515

RESUMO

BACKGROUND: Both allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts. METHODS: COSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD. RESULTS: Both in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12-2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32-3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy). CONCLUSION: These data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations.


Assuntos
Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Testes de Função Respiratória , Estudos Retrospectivos
19.
Clin Genet ; 101(1): 110-115, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34494659

RESUMO

The treatment of recessive dystrophic epidermolysis bullosa (RDEB) remains challenging. Elevated IgE levels have previously been reported in several RDEB patients. In this prospective, single-centre, open intervention study, elevated IgE levels were seen in 11 out of 12 patients with intense pruritus, and the patients with elevated IgE levels received anti-IgE therapy every 4 weeks for at least three cycles. Compared with the baseline, 10 patients with RDEB had good clinical outcomes with enhanced wound healing, a reduction in Birmingham (epidermolysis bullosa) EB severity score by 15%, a reduction in affected body surface area by 23.3%, amelioration of skin inflammation, and an increase in type VII collagen deposition by 13.1-fold. All the patients had a good tolerance to anti-IgE therapy. Furthermore, patients with higher IgE levels tended to have higher disease severity and more favorable clinical outcomes. Our report also suggested the potential role of IgE in the pathogenesis of inflammatory conditions associated with RDEB. (ChiCTR1900021437).


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Epidermólise Bolhosa Distrófica/tratamento farmacológico , Adolescente , Adulto , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Anti-Idiotípicos/efeitos adversos , Autoimunidade , Biópsia , Criança , Colágeno Tipo VII/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Epidermólise Bolhosa Distrófica/diagnóstico , Epidermólise Bolhosa Distrófica/etiologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele/imunologia , Pele/metabolismo , Pele/patologia , Resultado do Tratamento , Cicatrização , Adulto Jovem
20.
Clin Exp Dermatol ; 47(3): 547-552, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34655248

RESUMO

BACKGROUND: Allergy is increasingly reported by patients and members of the public, and there is evidence that the prevalence is increasing. Not all diagnoses have been made by clinicians, as direct-to-consumer (DTC) allergy tests are widely available online. AIM: To determine if DTC allergy tests are processed in accredited laboratories and utilize validated methods, while providing an overview of the DTC allergy tests available. METHODS: Internet searches using 'allergy test kit' and 'intolerance test' were performed to identify DTC food-allergy tests. Each company was contacted to enquire if they had ISO15189 accreditation, what methods of testing they used and what was the extent of individual clinical input used to guide the test requested or result interpretation. RESULTS: In total, 24 online companies providing DTC food-allergy testing were identified, of which 22 were contactable. One laboratory had ISO15189 accreditation, which was also the only laboratory using clinically recognized specific IgE testing and had a clinician involved in the process. Other laboratories used bioresonance or IgG and involved a nutritionist at most. CONCLUSION: Online DTC food-allergy tests are largely misleading to the consumer and provided by unaccredited laboratories using controversial methodology. The dermatologist must politely discount these results and assess the role of food allergy in a patient's skin disease on the merit of clinical history, supported by specific IgE testing as appropriate.


Assuntos
Triagem e Testes Direto ao Consumidor/normas , Hipersensibilidade Alimentar/diagnóstico , Acreditação , Comportamento do Consumidor , Humanos , Imunoglobulina E/sangue , Reino Unido
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