RESUMEN
BACKGROUND: Association of early pregnancy body mass index (BMI) and maternal gestational weight gain (GWG), and asthma and allergic disease in children is unclear. METHODS: We analyzed data from 3176 mother-child pairs in a prospective birth cohort study. Maternal anthropometric measurements in the first and last antenatal clinic visits were obtained through post-delivery questionnaires to calculate early pregnancy BMI and maternal GWG. Asthma and allergic diseases in children by the age of 5 years was assessed using a validated questionnaire. Furthermore, serum samples were analyzed for IgE antibodies to eight allergens. We applied Cox proportional hazards and logistic regression analyses to estimate the association of early pregnancy BMI and maternal GWG (as continuous variables and categorized into quarters), and asthma, atopic eczema, atopic sensitization, and allergic rhinitis in children. RESULTS: Neither early pregnancy BMI nor maternal GWG was associated with asthma and allergic disease in children when analyzed as continuous variables. However, compared to the first quarter of GWG (a rate <0.32 kg/week), mothers in the third quarter (rate 0.42-0.52 kg/week) had children with significantly higher odds of developing atopic eczema (adjusted OR 1.49, 95% CI [1.13-1.96]) by 5 years of age. CONCLUSION: Association of early pregnancy BMI and maternal GWG, and asthma and allergic disease in children, is inconsistent. High maternal GWG may be associated with increased odds of atopic eczema.
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Asma , Índice de Masa Corporal , Ganancia de Peso Gestacional , Hipersensibilidad , Humanos , Embarazo , Femenino , Asma/epidemiología , Asma/inmunología , Preescolar , Masculino , Estudios Prospectivos , Hipersensibilidad/epidemiología , Hipersensibilidad/inmunología , Adulto , Inmunoglobulina E/sangre , Lactante , Dermatitis Atópica/epidemiología , Dermatitis Atópica/inmunología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inmunología , Encuestas y Cuestionarios , Estudios de Cohortes , Cohorte de Nacimiento , Recién NacidoRESUMEN
Understanding the phenotypic and transcriptional signature of immunoglobulin E (IgE)-producing cells is fundamental to plasma cell (PC) biology and development of therapeutic interventions for allergy. Here, using a mouse model of intranasal house dust mite (HDM) exposure, we showed that short-lived IgE PCs emerge in lung draining lymph nodes (dLNs) during early exposure (<3 weeks) and long-lived IgE PCs accumulate in the bone marrow (BM) with prolonged exposure (>7 weeks). IgE PCs had distinct surface and gene expression profiles in these different tissues compared with other Ig isotypes. IgE BMPCs up-regulated genes associated with prosurvival and BM homing, whereas IgE dLN PCs expressed genes associated with recent class switching and differentiation. IgE PCs also exhibited higher expression of endoplasmic reticulum (ER) stress and protein coding genes and higher antibody secretion rate when compared with IgG1. Overall, this study highlights the unique developmental path and transcriptional signature of short-lived and long-lived IgE PCs.
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Inmunoglobulina E , Células Plasmáticas , Animales , Células Plasmáticas/inmunología , Inmunoglobulina E/inmunología , Ratones , Pyroglyphidae/inmunología , Ratones Endogámicos C57BL , Isotipos de Inmunoglobulinas/inmunología , Isotipos de Inmunoglobulinas/genética , FemeninoRESUMEN
Rationale: Food allergy is a prevalent disease in the U.S., affecting nearly 30 million people. The primary management strategy for this condition is food avoidance, as limited treatment options are available. The elevation of pathologic IgE and over-reactive mast cells/basophils is a central factor in food allergy anaphylaxis. This study aims to comprehensively evaluate the potential therapeutic mechanisms of a small molecule compound called formononetin in regulating IgE and mast cell activation. Methods: In this study, we determined the inhibitory effect of formononetin on the production of human IgE from peripheral blood mononuclear cells of food-allergic patients using ELISA. We also measured formononetin's effect on preventing mast cell degranulation in RBL-2H3 and KU812 cells using beta-hexosaminidase assay. To identify potential targets of formononetin in IgE-mediated diseases, mast cell disorders, and food allergies, we utilized computational modeling to analyze mechanistic targets of formononetin from various databases, including SEA, Swiss Target Prediction, PubChem, Gene Cards, and Mala Cards. We generated a KEGG pathway, Gene Ontology, and Compound Target Pathway Disease Network using these targets. Finally, we used qRT-PCR to measure the gene expression of selected targets in KU812 and U266 cell lines. Results: Formononetin significantly decreased IgE production in IgE-producing human myeloma cells and PBMCs from food-allergic patients in a dose-dependent manner without cytotoxicity. Formononetin decreased beta-hexosaminidase release in RBL-2H3 cells and KU812 cells. Formononetin regulates 25 targets in food allergy, 51 in IgE diseases, and 19 in mast cell diseases. KEGG pathway and gene ontology analysis of targets showed that formononetin regulated disease pathways, primary immunodeficiency, Epstein-Barr Virus, and pathways in cancer. The biological processes regulated by formononetin include B cell proliferation, differentiation, immune response, and activation processes. Compound target pathway disease network identified NFKB1, NFKBIA, STAT1, STAT3, CCND1, TP53, TYK2, and CASP8 as the top targets regulated at a high degree by formononetin. TP53, STAT3, PTPRC, IL2, and CD19 were identified as the proteins mostly targeted by formononetin. qPCR validated genes of Formononetin molecular targets of IgE regulation in U266 cells and KU812 cells. In U266 cells, formononetin was found to significantly increase the gene expression of NFKBIA, TP53, and BCL-2 while decreasing the gene expression of BTK TYK, CASP8, STAT3, CCND1, STAT1, NFKB1, IL7R. In basophils KU812 cells, formononetin significantly increased the gene expression of NFKBIA, TP53, and BCL-2 while decreasing the gene expression of BTK, TYK, CASP8, STAT3, CCND1, STAT1, NFKB1, IL7R. Conclusion: These findings comprehensively present formononetin's mechanisms in regulating IgE production in plasma cells and degranulation in mast cells.
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Hipersensibilidad a los Alimentos , Inmunoglobulina E , Isoflavonas , Quinasas Janus , Leucocitos Mononucleares , Mastocitos , Factores de Transcripción STAT , Transducción de Señal , Isoflavonas/farmacología , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina E/metabolismo , Mastocitos/inmunología , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Transcripción STAT/metabolismo , Quinasas Janus/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Femenino , Adulto , Degranulación de la Célula/efectos de los fármacos , Animales , Persona de Mediana EdadAsunto(s)
Proteínas Portadoras , Síndrome de Kounis , Humanos , Adolescente , Síndrome de Kounis/diagnóstico , Síndrome de Kounis/etiología , Proteínas Portadoras/efectos adversos , Proteínas Portadoras/inmunología , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/inmunología , Femenino , Masculino , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunologíaRESUMEN
As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3+ regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.
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Degranulación de la Célula , Dermatitis Atópica , Modelos Animales de Enfermedad , Mastocitos , Probióticos , Animales , Dermatitis Atópica/terapia , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Mastocitos/efectos de los fármacos , Probióticos/farmacología , Ratones , Degranulación de la Célula/efectos de los fármacos , Inmunoglobulina E/sangre , Ratones Endogámicos BALB C , Lactobacillus plantarum , Pyroglyphidae/inmunología , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Linfocitos T Reguladores/inmunología , QuimasasAsunto(s)
Absceso , Inmunoglobulina E , Síndrome de Job , Receptores de Interleucina-6 , Humanos , Síndrome de Job/diagnóstico , Síndrome de Job/inmunología , Inmunoglobulina E/sangre , Masculino , Femenino , Absceso/diagnóstico , Receptores de Interleucina-6/inmunología , Niño , Adolescente , PreescolarRESUMEN
Chronic spontaneous urticaria (CSU) is associated with skin mast cell activation, and its triggering mechanisms are not completely elucidated. Evidence suggests an autoimmune component of CSU. Our aim was to assess the usefulness of an autoimmune mast cell activation test (aiMAT) for diagnosing and differentiating CSU into different subtypes. We enrolled 43 patients with active, uncontrolled CSU before starting treatment with omalizumab and 15 controls. Patients were evaluated based on omalizumab response. aiMATs were performed using non-IgE-sensitized (NS) or myeloma IgE-sensitized (S) LAD2 cells, which were then stimulated with CSU/control sera (25 µL and 10 µL). The expression of CD63 was assessed with flow cytometry. CD63 response on NS-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.0007) and with 10 µL CSU/control sera (p = 0.0001). The ROC curve analysis demonstrated an area under the curve (AUC) of 0.82. The cutoff for autoimmune-non-IgE-sensitized-MAT was 40.3% CD63+ LAD2, which resulted in 73.3% sensitivity and 81.4% specificity. CD63 response on S-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.03). The ROC curve analysis demonstrated an AUC of 0.66. The cutoff for the autoimmune-myeloma IgE-sensitized-MAT was 58.4% CD63+ cells, which resulted in 62.8% sensitivity and 66.7% specificity. Overall, 36 out of 43 (84%) patients responded to omalizumab, and 7 (16%) were nonresponders. We found no differences between LAD2 CD63 response and response to omalizumab. In conclusion, aiMAT could represent a new diagnostic tool in CSU. Additional studies are needed to evaluate the potential benefits during omalizumab therapy.
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Urticaria Crónica , Mastocitos , Tetraspanina 30 , Humanos , Urticaria Crónica/diagnóstico , Urticaria Crónica/tratamiento farmacológico , Urticaria Crónica/inmunología , Urticaria Crónica/sangre , Femenino , Mastocitos/inmunología , Mastocitos/metabolismo , Masculino , Persona de Mediana Edad , Adulto , Tetraspanina 30/metabolismo , Omalizumab/uso terapéutico , Anciano , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Curva ROC , Estudios de Casos y ControlesRESUMEN
Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.
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Cannabinoides , Mieloma Múltiple , Telomerasa , Telómero , Proteína p53 Supresora de Tumor , Humanos , Mieloma Múltiple/tratamiento farmacológico , Línea Celular Tumoral , Telómero/efectos de los fármacos , Telómero/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Cannabinoides/farmacología , Telomerasa/metabolismo , Supervivencia Celular/efectos de los fármacos , FN-kappa B/metabolismo , Inmunoglobulina E , Inmunoglobulina G , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Bronchiolitis is a significant factor contributing to bronchial asthma in infants and young children. After treatment, recurrent wheezing symptoms often occur, especially in children with atopic constitution, who tend to have more severe conditions and poorer prognosis. Therefore, exploring the prognostic value of total serum immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) levels in children with atopic constitution who suffer from bronchiolitis is of great significance. A total of 260 children with bronchiolitis admitted to our hospital from October 2020 to June 2022 were regarded as the research subjects with prospective study, according to whether the children had atopic constitution, they were grouped into non atopic constitution group (n = 156) and atopic constitution group (n = 104); after 6 months of treatment, children with atopic constitution were grouped into a good prognosis group (n = 58) and a poor prognosis group (n = 46) based on their prognosis; in addition, 260 healthy children who underwent physical examination and had clinical data consistent with those of children with bronchiolitis were regarded as the reference group. The serum tIgE and FeNO levels of each group were compared; multivariate Logistic regression was applied to analyze the prognostic factors of children with atopic constitution bronchiolitis; ROC curve was applied to analyze the predictive value of tIgE and FeNO levels after treatment for the prognosis of children with atopic constitution bronchiolitis. The tIgE levels in the control group, non-atopic group, and atopic group [(123.54 ± 29.62) IU/mL, (245.71 ± 30.59) IU/mL, (316.46 ± 31.78) IU/mL, respectively] increased sequentially, with statistically significant differences (F = 1766.954, P = 0.000). The FeNO levels in the control group, non-atopic group, and atopic group [(8.36 ± 3.57) ppb, (15.28 ± 3.69) ppb, (19.84 ± 3.58) ppb, respectively] also increased sequentially, with statistically significant differences (F = 765.622, P = 0.000). The tIgE, FeNO, proportion of patients with asthma family history, and proportion of patients with allergic family history in the poor prognosis group were obviously higher than those in the good prognosis group (P < 0.05). Multivariate Logistic regression analysis showed that family history of asthma, family history of allergies, tIgE, and FeNO were influencing factors for the prognosis of children with atopic bronchiolitis (P < 0.05). The AUC of the combination of tIgE and FeNO in predicting the prognosis of children with atopic constitutional bronchiolitis was 0.910, with a sensitivity of 78.26% and a specificity of 93.10%, which was superior to the independent prediction of tIgE and FeNO (Zcombined detection-tIgE = 2.442, Zcombined detection-FeNO = 3.080, P = 0.015, 0.002). The levels of tIgE and FeNO in children with atopic constitution bronchiolitis are obviously increased, and the combination of the two has high predictive value for the prognosis of atopic constitution bronchiolitis.
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Bronquiolitis , Inmunoglobulina E , Óxido Nítrico , Humanos , Masculino , Femenino , Inmunoglobulina E/sangre , Pronóstico , Lactante , Óxido Nítrico/metabolismo , Óxido Nítrico/sangre , Bronquiolitis/sangre , Bronquiolitis/metabolismo , Estudios Prospectivos , Preescolar , Curva ROC , Biomarcadores/sangreRESUMEN
Neuromuscular blocking agents (NMBAs) relax skeletal muscles to facilitate surgeries and ease intubation but can lead to adverse reactions, including complications because of postoperative residual neuromuscular blockade (rNMB) and, in rare cases, anaphylaxis. Both adverse reactions vary between types of NMBAs, with rocuronium, a widely used nondepolarizing NMBA, inducing one of the longest rNMB durations and highest anaphylaxis incidences. rNMB induced by rocuronium can be reversed by the synthetic γ-cyclodextrin sugammadex. However, in rare cases, sugammadex can provoke anaphylaxis. Thus, additional therapeutic options are needed. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies. To understand the pathogenesis of rocuronium-induced anaphylaxis and to identify potential therapeutics, we investigated the memory B cell antibody repertoire of patients with suspected hypersensitivity to rocuronium. We identified polyclonal antibody repertoires with a high diversity among V(D)J genes without evidence of clonal groups. When recombinantly expressed, these antibodies demonstrated specificity and low affinity for rocuronium without cross-reactivity for other NMBAs. Moreover, when these antibodies were expressed as human immunoglobulin E (IgE), they triggered human mast cell activation and passive systemic anaphylaxis in transgenic mice, although their affinities were insufficient to serve as reversal agents. Rocuronium-specific, high-affinity antibodies were thus isolated from rocuronium-immunized mice. The highest-affinity antibody was able to reverse rocuronium-induced neuromuscular blockade in nonhuman primates with kinetics comparable to that of sugammadex. Together, these data support the hypothesis that antibodies cause anaphylactic reactions to rocuronium and pave the way for improved diagnostics and neuromuscular blockade reversal agents.
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Anafilaxia , Rocuronio , Rocuronio/efectos adversos , Animales , Humanos , Anafilaxia/inmunología , Anticuerpos , Ratones , Periodo Perioperatorio , Androstanoles/efectos adversos , Sugammadex/efectos adversos , Inmunoglobulina E/inmunología , Especificidad de Anticuerpos , Femenino , Modelos Animales de Enfermedad , MasculinoRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) on pediatric perennial allergic rhinitis (AR) based on longitudinal assessment of nasal symptoms, laboratory examination, and in vivo biomarkers. METHOD: The subjects included 40 children with perennial AR who had SLIT with HDM for 2 years. Nasal symptoms, medications, skin prick tests, nasal provocation tests, and peripheral blood tests were evaluated before, 6 months, one year and two years after the onset of SLIT. RESULTS: Total nasal symptom scores, prick test wheal diameter, and peripheral blood eosinophil count decreased in 6 months. Total nasal symptom scores continued to decrease from 6 months to 2 years. Symptom-medication scores and nasal provocation test responses decreased in 1 year. Symptom-medication scores continued to decline from 1 to 2 years. Medication scores and nasal eosinophilia decreased in 2 years. Serum specific IgE to HDM slightly increased transiently and decreased in 2 years. The severity of symptoms and specific IgE to HDM at the baseline, and changes of symptoms and specific IgE to HDM during the first six months and first one year of SLIT were correlated with improvement in symptom scores over two years of SLUT. TNSS at baseline was correlated with that at second year. CONCLUSION: Longitudinal assessment of symptoms, allergen specific IgE, and in vivo biomarkers showed the effectiveness of SLIT. Symptom scores and allergen specific IgE may also be early predictive factors of SLIT efficacy in children with AR.
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Biomarcadores , Inmunoterapia Sublingual , Humanos , Niño , Biomarcadores/sangre , Masculino , Femenino , Estudios Longitudinales , Rinitis Alérgica Perenne/terapia , Rinitis Alérgica Perenne/inmunología , Rinitis Alérgica Perenne/diagnóstico , Pyroglyphidae/inmunología , Animales , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Adolescente , PreescolarRESUMEN
Atopic dermatitis (AD) and food allergies are 2 atopic conditions that tend to develop early in life. Their interrelationship has been a topic of controversy and many studies. The presence of atopic dermatitis in infancy and early childhood, particularly if severe, is a risk factor for the development of immunoglobulin E (IgE) -mediated food allergies. While it is common for children with AD to demonstrate extensive sensitization to foods, serum IgE testing is not always indicative of clinical allergy.
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Dermatitis Atópica , Hipersensibilidad a los Alimentos , Inmunoglobulina E , Humanos , Dermatitis Atópica/inmunología , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/complicaciones , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Factores de Riesgo , LactanteRESUMEN
Allergic rhinitis (AR) is a chronic, non-infectious inflammatory condition of the nasal mucosa mediated by IgE. There is a need for the development of novel medications to treat this ailment. Isoorientin is a naturally occurring flavonoid that possesses antioxidant, anti--inflammatory, and various other advantageous characteristics. However, its potential effects on AR remain unclear. This study evaluates the therapeutic effects of isoorientin on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice and explores the underlying mechanism. Our study revealed that isoorientin administration effectively decreased the frequency of nose rubbing and sneezing in AR mice. The groups treated with isoorientin showed a significant decrease in serum levels of IgE and histamine, with reductions of 40% and 30%, respectively. Isoorientin ameliorated inflammation of the nasal mucosa and restored the Th1/Th2 balance. In addition, isoorientin inhibited the activation of the NF-κB pathway in nasal tissues. In summary, Isoorientin alleviates OVA-stimulated AR in mice by restoring Th1/Th2 balance and blocking the NF-κB pathway. Thus, isoorientin exhibits promise as a natural therapeutic agent for allergic rhinitis.
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Modelos Animales de Enfermedad , Inmunoglobulina E , Luteolina , Ratones Endogámicos BALB C , FN-kappa B , Mucosa Nasal , Ovalbúmina , Rinitis Alérgica , Balance Th1 - Th2 , Animales , Luteolina/farmacología , Ovalbúmina/inmunología , Ratones , Rinitis Alérgica/inmunología , Rinitis Alérgica/tratamiento farmacológico , Balance Th1 - Th2/efectos de los fármacos , Mucosa Nasal/inmunología , Mucosa Nasal/efectos de los fármacos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , FN-kappa B/metabolismo , Células Th2/inmunología , Femenino , Humanos , Alérgenos/inmunología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Células TH1/inmunología , Células TH1/efectos de los fármacos , Histamina/metabolismo , Histamina/sangreRESUMEN
Allergic asthma is an important public health problem and is a complicated respiratory sickness that is characterized by bronchial inflammation, bronchoconstriction, and breathlessness. Asthma is orchestrated by type 2 immune response and remodeling is one of the important outputted problem in chronic asthma. Thymol is a naturally occurring monocyclic phenolic, it has a series of biological properties, and its immunomodulatory and anti-remodeling effects on allergic asthma were evaluated. The OVA-LPS-induced asthmatic mice were treated with thymol. Methacholine challenge test, eosinophil count, and levels of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, total and OVA-specific IgE levels in serum, remodeling factors, gene expression of TGF-ß, Smad2, Smad3, and lung histopathology were done. Treatment with thymol could control AHR, eosinophil percentage levels of Th2 cytokines and Igs, remodeling factors, expression of TGF-ß, Smad2 and Smad3 genes, inflammation, goblet cell hyperplasia, and mucus production in asthmatic mice. Thymol can control asthma pathogens and related remodeling and fibrosis bio-factors and can be a potential treatment of asthma.
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Remodelación de las Vías Aéreas (Respiratorias) , Asma , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Transducción de Señal , Proteína smad3 , Timol , Factor de Crecimiento Transformador beta , Animales , Timol/farmacología , Asma/inmunología , Asma/tratamiento farmacológico , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Proteína smad3/metabolismo , Ratones , Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Citocinas/metabolismo , Femenino , Ovalbúmina/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Eosinófilos/inmunología , Eosinófilos/efectos de los fármacos , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Proteína Smad2/metabolismoRESUMEN
Systemic mastocytosis (SM) is a clonal mast cell disorder that can lead to potentially severe anaphylactic reactions. Hymenoptera sting is one of the most frequent triggers of anaphylaxis in these patients, and diagnosis of indolent SM (ISM) without skin involvement (ISMs) is not rare. In this subgroup of patients, venom immunotherapy (VIT) is an effective treatment decreasing subsequent systemic reactions, and lifelong administration is recommended. An individualized diagnosis is necessary to offer the most adequate VIT, and molecular diagnosis (MD) may be useful to discriminate between primary sensitization and cross-reactivity. Nevertheless, other techniques such as ImmunoCAP inhibition assays may be necessary to identify the genuine sensitization to offer the most suitable VIT. We present a male patient with an anaphylactic reaction following several wasp stings. The patient was diagnosed with ISM, and allergy to both Polistes dominula and Vespula sp venom was confirmed. In this scenario, MD did not discriminate between a genuine double sensitization and venom cross-reactivity between both vespids. Thus, CAP-inhibition assay was performed. This case indicated the importance of an accurate diagnosis of hymenoptera venom allergy (HVA). It also highlights the usefulness of CAP-inhibition assays when MD fails to distinguish between genuine double Polistes-Vespula sensitization and cross-reactivity.
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Anafilaxia , Reacciones Cruzadas , Mordeduras y Picaduras de Insectos , Mastocitosis Sistémica , Venenos de Avispas , Avispas , Humanos , Masculino , Venenos de Avispas/inmunología , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/inmunología , Mastocitosis Sistémica/complicaciones , Animales , Anafilaxia/diagnóstico , Anafilaxia/inmunología , Anafilaxia/etiología , Mordeduras y Picaduras de Insectos/inmunología , Mordeduras y Picaduras de Insectos/diagnóstico , Mordeduras y Picaduras de Insectos/complicaciones , Avispas/inmunología , Reacciones Cruzadas/inmunología , Desensibilización Inmunológica/métodos , Alérgenos/inmunología , Alérgenos/administración & dosificación , Triptasas/sangre , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangreAsunto(s)
Anafilaxia , Citrus sinensis , Hipersensibilidad a los Alimentos , Giberelinas , Humanos , Anafilaxia/diagnóstico , Anafilaxia/etiología , Anafilaxia/inmunología , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/diagnóstico , Citrus sinensis/inmunología , Citrus sinensis/efectos adversos , Giberelinas/efectos adversos , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Proteínas de Plantas/inmunología , Proteínas de Plantas/efectos adversos , Femenino , Masculino , Alérgenos/inmunología , Alérgenos/efectos adversos , Antígenos de Plantas/inmunología , Pruebas CutáneasRESUMEN
OBJECTIVES: This thesis aims to provide patients with a preventive and therapeutic basis by analyzing IgE level influencing factors of common allergens for Allergic Rhinitis (AR). METHOD: Multiple linear regression analysis is made upon questionnaires among 749 cases of AR patients that are divided into 5 age-based groups. Perform serum-specific IgE content testing on patients. RESULTS: Cockroach being an allergen, AR patients' IgE Level is influenced by allergic history, home-raised plants and animals. For AR patients with mugwort as an allergen, allergy and asthma history could increase IgE level, respectively, ß = 4.291 and ß = 4.364. If the allergen turns out to be peanut, allergic history would increase the IgE level (ß = 0.171), however, the level would be lower in female patients compared with male patients (ß = -0.078). For patients with egg as an allergen, allergic history, home-raised plants and animals (pets) would all affect the IgE level, respectively, ß = 0.182, ß = 0.118 and ß = -0.101. CONCLUSIONS: IgE level varies according to allergic history, home-raised plants & animals, gender, furniture renewal, asthma, and ages for patients with different allergens including cockroach, mold, mugwort, peanut, egg and crab. For each kind of allergen, the IgE levels react differently to different influencing factors, thus requiring a thorough analysis of each AR patient's allergen and allergenic factors.
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Alérgenos , Inmunoglobulina E , Rinitis Alérgica , Humanos , Femenino , Inmunoglobulina E/sangre , Masculino , Alérgenos/inmunología , China/epidemiología , Adulto , Niño , Adolescente , Adulto Joven , Rinitis Alérgica/inmunología , Rinitis Alérgica/sangre , Animales , Persona de Mediana Edad , Preescolar , Factores Sexuales , Factores de Edad , Encuestas y Cuestionarios , AncianoRESUMEN
BACKGROUND: Cross-reactivity between nonspecific lipid transfer proteins could cause anaphylaxis, further influencing food avoidance and nutrient deficiencies. The one affecting olive pollen (Ole e 7) and peach (Pru p 3) may underlie a variety of pollen-food syndromes, though a deep molecular analysis is necessary. METHODS: Three Ole e 7-monosensitised patients (MON_OLE), three Pru p 3-monosensitised patients (MON_PRU) and three bisensitised patients (BI) were selected. For epitope mapping, both digested proteins were incubated with patient sera, and the captured IgE-bound peptides were characterised by LC-MS. RESULTS: The analysis revealed two Ole e 7 epitopes and the three Pru p 3 epitopes previously described. Interestingly, the "KSALALVGNKV" Ole e 7 peptide was recognised by MON_OLE, BI and MON_PRU patients. Conversely, all patients recognised the "ISASTNCATVK" Pru p 3 peptide. Although complete sequence alignment between both proteins revealed 32.6% identity, local alignment considering seven residue fragments showed 50 and 57% identity when comparing "ISASTNCATVK" with Ole e 7 and "KSALALVGNKV" with Pru p 3. CONCLUSIONS: This study mapped sIgE-Ole e 7-binding epitopes, paving the way for more precise diagnostic tools. Assuming non-significant sequence similarity, structural homology and shared key residues may underlie the potential cross-reactivity between Ole e 7 and Pru p 3 nsLTPs.
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Antígenos de Plantas , Reacciones Cruzadas , Hipersensibilidad a los Alimentos , Inmunoglobulina E , Olea , Proteínas de Plantas , Polen , Prunus persica , Humanos , Antígenos de Plantas/inmunología , Hipersensibilidad a los Alimentos/inmunología , Polen/inmunología , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Olea/inmunología , Proteínas de Plantas/inmunología , Femenino , Masculino , Prunus persica/inmunología , Mapeo Epitopo , Adulto , Rinitis Alérgica Estacional/inmunología , Secuencia de Aminoácidos , Epítopos/inmunología , Alérgenos/inmunología , Persona de Mediana Edad , Proteínas Portadoras/inmunologíaRESUMEN
PURPOSE OF REVIEW: There is growing evidence that enolase is involved in allergy. This manuscript reviews the impact of enolase in allergic disease and describes several sources of this allergen including molds, plants, animals, and pollens, among others. IgE epitopes are carefully analyzed as they may account for cross-reactivity. RECENT FINDINGS: Enolase has been previously associated to food allergy and contact dermatitis. However, other groups and we have identified recently novel enolases derived from diverse pollens in patients suffering asthma and allergic rhinitis. Exposure to outdoor enolases may cause respiratory disease. Enolase has been identified across various species and its amino acid sequence is highly conserved among different sources of this allergen. The demonstration that enolase is involved in many allergic diseases including respiratory allergies, is of clinic relevance. Thus, the development of novel molecular-based diagnostic and therapeutic strategies may pave the way for improved diagnosis and therapeutics.
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Alérgenos , Hipersensibilidad , Fosfopiruvato Hidratasa , Humanos , Fosfopiruvato Hidratasa/inmunología , Animales , Alérgenos/inmunología , Hipersensibilidad/inmunología , Reacciones Cruzadas/inmunología , Inmunoglobulina E/inmunología , Polen/inmunologíaRESUMEN
Humoral response to SARS-CoV-2 has been studied, predominantly the classical IgG and its subclasses. Although IgE antibodies are typically specific to allergens or parasites, a few reports describe their production in response to SARS-CoV-2 and other viruses. Here, we investigated IgE specific to receptor binding domain (RBD) of SARS-CoV-2 in a Brazilian cohort following natural infection and vaccination. Samples from 59 volunteers were assessed after infection (COVID-19), primary immunization with vectored (ChAdOx1) or inactivated (CoronaVac) vaccines, and booster immunization with mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased its levels. Subjects vaccinated with two doses of ChAdOx1 exhibited a more robust response than those immunized with two doses of CoronaVac; however, after boosting with BNT162b2, all groups presented similar IgE levels. IgE showed intermediate-to-high avidity, especially after the booster vaccine. We also found IgG4 antibodies, mainly after the booster, and they moderately correlated with IgE. ELISA results were confirmed by control assays, using IgG depletion by protein G and lack of reactivity with heterologous antigen. In our cohort, no clinical data could be associated with the IgE response. We advocate for further research on IgE and its role in viral immunity, extending beyond allergies and parasitic infections.