RESUMO
Pollen from common ragweed is an important allergen source worldwide and especially in western and southern Romania. More than 100 million patients suffer from symptoms of respiratory allergy (e.g., rhinitis, asthma) to ragweed pollen. Among the eleven characterized allergens, Amb a 6 is a non-specific lipid transfer protein (nsLTP). nsLTPs are structurally stable proteins in pollen and food from different unrelated plants capable of inducing severe reactions. The goal of this study was to produce Amb a 6 as a recombinant and structurally folded protein (rAmb a 6) and to characterize its physicochemical and immunological features. rAmb a 6 was expressed in Spodoptera frugiperda Sf9 cells as a secreted protein and characterized by mass spectrometry and circular dichroism (CD) spectroscopy regarding molecular mass and fold, respectively. The IgE-binding frequency towards the purified protein was evaluated using sera from 150 clinically well-characterized ragweed-allergic patients. The allergenic activities of rAmb a 6 and the nsLTP from the weed Parietaria judaica (Par j 2) were evaluated in basophil activation assays. rAmb a 6-specific IgE reactivity was associated with clinical features. Pure rAmb a 6 was obtained by insect cell expression. Its deduced molecular weight corresponded to that determined by mass spectrometry (i.e., 10,963 Da). rAmb a 6 formed oligomers as determined by SDS-PAGE under non-reducing conditions. According to multiple sequence comparisons, Amb a 6 was a distinct nsLTP with less than 40% sequence identity to currently known plant nsLTP allergens, except for nsLTP from Helianthus (i.e., 52%). rAmb a 6 is an important ragweed allergen recognized by 30% of ragweed pollen allergic patients. For certain patients, rAmb a 6-specific IgE levels were higher than those specific for the major ragweed allergen Amb a 1 and analysis also showed a higher allergenic activity in the basophil activation test. rAmb a 6-positive patients suffered mainly from respiratory symptoms. The assumption that Amb a 6 is a source-specific ragweed allergen is supported by the finding that none of the patients showing rAmb a 6-induced basophil activation reacted with Par j 2 and only one rAmb a 6-sensitized patient had a history of plant food allergy. Immunization of rabbits with rAmb a 6 induced IgG antibodies which strongly inhibited IgE binding to rAmb a 6. Our results demonstrate that Amb a 6 is an important source-specific ragweed pollen allergen that should be considered for diagnosis and allergen-specific immunotherapy of ragweed pollen allergy.
Assuntos
Alérgenos , Antígenos de Plantas , Proteínas de Transporte , Imunoglobulina E , Humanos , Alérgenos/imunologia , Imunoglobulina E/imunologia , Antígenos de Plantas/imunologia , Antígenos de Plantas/química , Animais , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo , Proteínas de Plantas/imunologia , Proteínas de Plantas/química , Feminino , Rinite Alérgica Sazonal/imunologia , Masculino , Adulto , Ambrosia/imunologia , Spodoptera/imunologia , Proteínas Recombinantes/imunologia , Sequência de Aminoácidos , Células Sf9 , Pessoa de Meia-Idade , Extratos VegetaisRESUMO
Common ragweed pollen allergy has become a health burden worldwide. One of the major allergens in ragweed allergy is Amb a 1, which is responsible for over 90% of the IgE response in ragweed-allergic patients. The major allergen isoform Amb a 1.01 is the most allergenic isoform in ragweed pollen. So far, no recombinant Amb a 1.01 with similar allergenic properties to its natural counterpart (nAmb a 1.01) has been produced. Hence, this study aimed to produce a recombinant Amb a 1.01 with similar properties to the natural isoform for improved ragweed allergy management. Amb a 1.01 was expressed in insect cells using a codon-optimized DNA construct with a removable N-terminal His-Tag (rAmb a 1.01). The recombinant protein was purified by affinity chromatography and physicochemically characterized. The rAmb a 1.01 was compared to nAmb a 1.01 in terms of the IgE binding (enzyme-linked immunosorbent assay (ELISA), immunoblot) and allergenic activity (mediator release assay) in well-characterized ragweed-allergic patients. The rAmb a 1.01 exhibited similar IgE reactivity to nAmb a 1.01 in different IgE-binding assays (i.e., IgE immunoblot, ELISA, quantitative ImmunoCAP inhibition measurements). Furthermore, the rAmb a 1.01 showed comparable dose-dependent allergenic activity to nAmb a 1.01 regarding basophil activation. Overall, the results showed the successful expression of an rAmb a 1.01 with comparable characteristics to the corresponding natural isoform. Our findings provide the basis for an improvement in ragweed allergy research, diagnosis, and immunotherapy.
Assuntos
Alérgenos , Ambrosia , Antígenos de Plantas , Imunoglobulina E , Proteínas Recombinantes , Humanos , Antígenos de Plantas/imunologia , Antígenos de Plantas/genética , Antígenos de Plantas/química , Imunoglobulina E/imunologia , Animais , Alérgenos/imunologia , Alérgenos/genética , Ambrosia/imunologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Feminino , Adulto , Proteínas de Plantas/imunologia , Proteínas de Plantas/genética , Proteínas de Plantas/química , Rinite Alérgica Sazonal/imunologia , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/químicaRESUMO
BACKGROUND: House dust mite (HDM) allergens are major elicitors of allergic reactions worldwide. OBJECTIVE: Identification, characterization, and evaluation of diagnostic utility of a new important HDM allergen was performed. METHODS: A cDNA coding for a new Dermatophagoides pteronyssinus (Dp) allergen, Der p 37, was isolated from a Dp expression library with allergic patients' IgE antibodies. Recombinant Der p 37 (rDer p 37) expressed in Escherichia coli was purified, then characterized by mass spectrometry, circular dichroism, and IgE reactivity by ImmunoCAP ISAC technology with sera from 111 clinically defined HDM-allergic patients. The allergenic activity of rDer p 37 was studied by basophil activation and CD4+ T-cell responses by carboxyfluorescein diacetate succinimidyl ester dilution assays. Specific antibodies raised against rDer p 37 were used for the ultrastructural localization of Der p 37 in mites by immunogold transmission electron microscopy. RESULTS: Der p 37, a 26 kDa allergen with homology to chitin-binding proteins, is immunologically distinct from Der p 15, 18, and 23. It is located in the peritrophic membrane of fecal pellets. Der p 37 reacted with IgE antibodies from a third of HDM-allergic patients and induced specific basophil- and CD4+ T-cell activation. Der p 37 IgE-positive patients had significantly higher IgE levels to major HDM allergens, reacted with more HDM allergens, and had a higher risk (odds ratio = 3.1) of asthma compared to Der p 37-negative patients. CONCLUSIONS: Der p 37, a new Dp allergen recognized by a third of HDM-allergic patients, may serve as a surrogate marker for severe HDM sensitization and asthma.
Assuntos
Asma , Hipersensibilidade , Alérgenos , Animais , Antígenos de Dermatophagoides , Proteínas de Artrópodes , Asma/diagnóstico , Poeira , Escherichia coli/genética , Humanos , Imunoglobulina E , PyroglyphidaeRESUMO
BACKGROUND: Worldwide, pollen of the weed mugwort (Artemisiavulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and the corresponding HLA have been made. OBJECTIVE: We sought to characterize IgE epitopes of Art v 1-sensitized patients and humanized mice for molecular immunotherapy of mugwort allergy. METHODS: Four overlapping peptides incorporating surface-exposed amino acids representing the full-length Art v 1 sequence were synthesized and used to search for IgE reactivity to sequential epitopes. For indirect mapping, peptide-specific rabbit antibodies were raised to block IgE against surface-exposed epitopes on folded Art v 1. IgE reactivity and basophil activation studies were performed in clinically defined mugwort-allergic patients. Secondary structure of recombinant (r) Art v 1 and peptides was determined by circular dichroism spectroscopy. RESULTS: Mugwort-allergic patients and humanized mice sensitized by allergen inhalation showed IgE reactivity and/or basophil activation mainly to folded, complete Art v 1 but not to unfolded, sequential peptide epitopes. Blocking of allergic patients' IgE with peptide-specific rabbit antisera identified a hitherto unknown major conformational IgE binding site in the C-terminal Art v 1 domain. CONCLUSIONS: Identification of the new major conformational IgE binding site on Art v 1, which can be blocked with IgG raised against non-IgE reactive Art v 1 peptides, is an important basis for the development of a hypoallergenic peptide vaccine for mugwort allergy.
Assuntos
Artemisia , Hipersensibilidade , Alérgenos , Aminoácidos , Animais , Antígenos de Plantas , Artemisia/química , Epitopos de Linfócito T , Humanos , Soros Imunes , Imunoglobulina E , Imunoglobulina G , Camundongos , Peptídeos , Proteínas de Plantas , CoelhosRESUMO
Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization.
Assuntos
Alérgenos , Hipersensibilidade , Humanos , Alérgenos/química , Profilinas , Cálcio , Proteínas de Plantas , Antígenos de Plantas , Extratos Vegetais , Reações Cruzadas , Imunoglobulina E/metabolismo , Ambrosia/metabolismoRESUMO
Myoblast fusion is required for myotube formation during myogenesis, and defects in myoblast differentiation and fusion have been implicated in a number of diseases, including human rhabdomyosarcoma. Although transcriptional regulation of the myogenic program has been studied extensively, the mechanisms controlling myoblast fusion remain largely unknown. This study identified and characterized the dynamics of a distinct class of blebs, termed bubbling blebs, which are smaller than those that participate in migration. The formation of these bubbling blebs occurred during differentiation and decreased alongside a decline in phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) at the plasma membrane before myoblast fusion. In a human rhabdomyosarcoma-derived (RD) cell line that exhibits strong blebbing dynamics and myoblast fusion defects, PIP3 was constitutively abundant on the membrane during myogenesis. Targeting phosphatase and tensin homolog (PTEN) to the plasma membrane reduced PIP3 levels, inhibited bubbling blebs and rescued myoblast fusion defects in RD cells. These findings highlight the differential distribution and crucial role of PIP3 during myoblast fusion and reveal a novel mechanism underlying myogenesis defects in human rhabdomyosarcoma.
Assuntos
Desenvolvimento Muscular , Rabdomiossarcoma , Diferenciação Celular , Fusão Celular , Humanos , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas , Mioblastos , Rabdomiossarcoma/genéticaRESUMO
IMPORTANCE: Patients with schizophrenia tend to have severe deficits in theory of mind, which may limit their interpretation of others' behaviors and thereby hamper social participation. Commonly used measures of theory of mind assess the ability to understand various social situations (e.g., implied meaning or hinting, faux pas), but these measures do not yield valid, reliable, and gender unbiased results to inform interventions for managing theory-of-mind deficits. We used understanding of implied meaning, which appears to be a unidimensional construct highly correlated with social competence, as a promising starting point to develop a theory-of-mind assessment. OBJECTIVE: To develop a Rasch-calibrated computerized test of implied meaning. DESIGN: Cross-sectional design. SETTING: Psychiatric hospitals and community. PARTICIPANTS: 344 participants (240 patients with schizophrenia and 104 healthy adults). RESULTS: We initially developed 27 items for the Computerized Implied Meaning Test. After inappropriate items (12 misfit items and 1 gender-biased item) were removed, the remaining 14 items showed acceptable model fit to the Rasch model (infit = 0.84-1.16; outfit = 0.65-1.34) and the one-factor model (comparative fit index = .91, standardized root mean square residual = .05, root-mean-square error of approximation = .08). Most patients (81.7%) achieved individual Rasch reliability of ≥.90. Healthy participants performed significantly better on the test than patients with schizophrenia (Cohen's d = 2.5, p < .001). CONCLUSIONS AND RELEVANCE: Our preliminary findings suggest that the Computerized Implied Meaning Test may provide reliable, valid, and gender-unbiased results for patients with schizophrenia. What This Article Adds: We developed a new measure for assessing theory-of-mind ability in patients with schizophrenia that consists of items targeting the understanding of implied meaning. Preliminary findings suggest that the Computerized Implied Meaning Test is reliable, valid, and gender unbiased and may be used in evaluating patients' theory-of-mind deficits and relevant factors.
Assuntos
Esquizofrenia , Adulto , Estudos Transversais , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
We investigate oscillations in coupled systems. The methodology is based on the Hopf bifurcation theorem and a condition extended from the Routh-Hurwitz criterion. Such a condition leads to locating the bifurcation values of the parameters. With such an approach, we analyze a single-cell system modeling the minimal genetic negative feedback loop and the coupled-cell system composed by these single-cell systems. We study the oscillatory properties for these systems and compare these properties between the model with Hill-type repression and the one with protein-sequestration-based repression. As the parameters move from the Hopf bifurcation value for single cells to the one for coupled cells, we compute the eigenvalues of the linearized systems to obtain the magnitude of the collective frequency when the periodic solution of the coupled-cell system is generated. Extending from this information on the parameter values, we further compute and compare the collective frequency for the coupled-cell system and the average frequency of the decoupled individual cells. To compare these scenarios with other biological oscillators, we perform parallel analysis and computations on a segmentation clock model.
Assuntos
Relógios Biológicos , Conceitos Matemáticos , RetroalimentaçãoRESUMO
BACKGROUND: Fluid intelligence deficits affect executive functioning and social behaviors in patients with schizophrenia. To help clinicians manage fluid intelligence deficits, a psychometrically sound measure is needed. The purposes of this study were to examine the test-retest reliability and convergent validity of the Test of Nonverbal Intelligence-Fourth Edition (TONI-4) assessing fluid intelligence in patients with schizophrenia. METHODS: A total of 103 patients with stable condition were assessed with the TONI-4 twice with a 4-week interval to examine the test-retest reliability. We further used the Montreal Cognitive Assessment (MoCA) and the Tablet-Based Symbol Digit Modalities Test (T-SDMT) to examine the convergent validity of the TONI-4. RESULTS: The intra-class correlation coefficient was 0.73 for the TONI-4. The percentages of standard error of measurement and minimal detectable change for the TONI-4 were 5.1 and 14.2%, respectively. The practice effect of the TONI-4 was small (Cohen's d = - 0.03). Convergent validity showed small to moderate significant correlations between the TONI-4 and the MoCA as well as the T-SDMT (r = 0.35, p = .011 with the T-SDMT and r = 0.61, p < .001 with the MoCA). The results demonstrated that the TONI-4 had good test-retest reliability, limited random measurement error, and a trivial practice effect. The convergent validity of the TONI-4 was good. CONCLUSIONS: These findings indicate that the TONI-4 has potential to be a reliable and valid assessment of fluid intelligence in patients with schizophrenia.
Assuntos
Esquizofrenia , Humanos , Inteligência , Testes de Estado Mental e Demência , Testes Neuropsicológicos , Psicometria , Reprodutibilidade dos Testes , Esquizofrenia/diagnósticoRESUMO
Extremely low-frequency electromagnetic field (ELF-EMF) exposures influence many biological systems. These effects are mainly related to the intensity, duration, frequency, and pattern of the ELF-EMF. Our intent was to characterize the effect of specific pulsed electromagnetic fields on the in vitro proliferation of MCF-7 adenocarcinoma and MDA-MB-231 breast cancer cell lines and one non-cancerous M10 breast epithelial cell line. The following four important parameters of ELF-EMF were examined: frequencies (7.83 ± 0.3, 23.49 ± 0.3, and 39.15 ± 0.3 Hz), flux density (0.5 and 1 mT), exposure duration (12, 24, and 48 h), and the exposure methodology (continuous exposure versus switching exposure). The viability of MDA-MB-231 cells exposed to the optimized ELF-EMF pattern (7.83 ± 0.3 Hz, 1 mT, and 6 h switching exposure) was 40.1%. By contrast, the optimized ELF-EMF parameters that were most cytotoxic to breast cancer MDA-MB-231 cells were not damaging to normal M10 cells. In vitro studies also showed that exposure of MDA-MB-231 cells to the optimized ELF-EMF pattern promoted Ca2+ influx and resulted in apoptosis. These data confirm that exposure to this specific ELF-EMF pattern can influence cellular processes and inhibit cancer cell growth. The specific ELF-EMF pattern determined in this study may provide a potential anti-cancer treatment in the future.
Assuntos
Neoplasias da Mama , Campos Eletromagnéticos , Apoptose , Proliferação de Células , Feminino , Humanos , Células MCF-7RESUMO
Long non-coding RNAs (lncRNAs) have gained increasing attention as they exhibit highly tissue- and cell-type specific expression patterns. LncRNAs are highly expressed in the central nervous system and their roles in the brain have been studied intensively in recent years, but their roles in the spinal motor neurons (MNs) are largely unexplored. Spinal MN development is controlled by precise expression of a gene regulatory network mediated spatiotemporally by transcription factors, representing an elegant paradigm for deciphering the roles of lncRNAs during development. Moreover, many MN-related neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are associated with RNA metabolism, yet the link between MN-related diseases and lncRNAs remains obscure. In this review, we summarize lncRNAs known to be involved in MN development and disease, and discuss their potential future therapeutic applications.
Assuntos
Esclerose Lateral Amiotrófica/genética , Neurônios Motores/fisiologia , Atrofia Muscular Espinal/genética , RNA Longo não Codificante/genética , Animais , Humanos , Camundongos , Doenças Neurodegenerativas/genéticaRESUMO
BACKGROUND: In the house dust mite (HDM) Dermatophagoides pteronyssinus, Der p 1, 2, 5, 7, 21, and 23 have been identified as the most important allergens. The aim of this study was to define hypoallergenic peptides derived from the sequences of the six allergens and to use the peptides and the complete allergens to study antibody, T cell, and cytokine responses in sensitized and nonsensitized subjects. METHODS: IgE reactivity of HDM-allergic and non-HDM-sensitized individuals to 15 HDM allergens was established using ImmunoCAP ISAC technology. Thirty-three peptides covering the sequences of the six HDM allergens were synthesized. Allergens and peptides were tested for IgE and IgG reactivity by ELISA and ImmunoCAP, respectively. Allergenic activity was determined by basophil activation. CD4+ T cell and cytokine responses were determined in PBMC cultures by CFSE dilution and Luminex technology, respectively. RESULTS: House dust mite allergics showed IgE reactivity only to complete allergens, whereas 31 of the 33 peptides lacked relevant IgE reactivity and allergenic activity. IgG antibodies of HDM-allergic and nonsensitized subjects were directed against peptide epitopes and higher allergen-specific IgG levels were found in HDM allergics. PBMC from HDM-allergics produced higher levels of IL-5 whereas non-HDM-sensitized individuals mounted higher levels of IFN-gamma, IL-17, pro-inflammatory cytokines, and IL-10. CONCLUSION: IgG antibodies in HDM-allergic patients recognize peptide epitopes which are different from the epitopes recognized by IgE. This may explain why naturally occurring allergen-specific IgG antibodies do not protect against IgE-mediated allergic inflammation. A mix of hypoallergenic peptides containing T cell epitopes of the most important HDM allergens was identified.
Assuntos
Alérgenos/imunologia , Epitopos de Linfócito T/imunologia , Hipersensibilidade/imunologia , Peptídeos/imunologia , Pyroglyphidae/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Estudos de Casos e Controles , Cisteína Endopeptidases/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologiaRESUMO
Ambrosia artemisiifolia, also known as common or short ragweed, is an invasive annual flowering herbaceous plant that has its origin in North America. Nowadays, ragweed can be found in many areas worldwide. Ragweed pollen is known for its high potential to cause type I allergic reactions in late summer and autumn and represents a major health problem in America and several countries in Europe. Climate change and urbanization, as well as long distance transport capacity, enhance the spread of ragweed pollen. Therefore ragweed is becoming domestic in non-invaded areas which in turn will increase the sensitization rate. So far 11 ragweed allergens have been described and, according to IgE reactivity, Amb a 1 and Amb a 11 seem to be major allergens. Sensitization rates of the other allergens vary between 10 and 50%. Most of the allergens have already been recombinantly produced, but most of them have not been characterized regarding their allergenic activity, therefore no conclusion on the clinical relevance of all the allergens can be made, which is important and necessary for an accurate diagnosis. Pharmacotherapy is the most common treatment for ragweed pollen allergy but fails to impact on the course of allergy. Allergen-specific immunotherapy (AIT) is the only causative and disease-modifying treatment of allergy with long-lasting effects, but currently it is based on the administration of ragweed pollen extract or Amb a 1 only. In order to improve ragweed pollen AIT, new strategies are required with higher efficacy and safety.
Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Hipersensibilidade/terapia , Extratos Vegetais/imunologia , Efeitos Psicossociais da Doença , Dessensibilização Imunológica , Humanos , Hipersensibilidade/economia , Proteínas de Plantas/imunologiaRESUMO
Somitogenesis is the process for the development of somites in vertebrate embryos. This process is timely regulated by synchronous oscillatory expression of the segmentation clock genes. Mathematical models expressed by delay equations or ODEs have been proposed to depict the kinetics of these genes in interacting cells. Through mathematical analysis, we investigate the parameter regimes for synchronous oscillations and oscillation-arrested in an ODE model and a model with transcriptional and translational delays, both with Michaelis-Menten type degradations. Comparisons between these regimes for the two models are made. The delay model has larger capacity to accommodate synchronous oscillations. Based on the analysis and numerical computations extended from the analysis, we explore how the periods and amplitudes of the oscillations vary with the degradation rates, synthesis rates, and coupling strength. For typical parameter values, the period and amplitude increase as some synthesis rate or the coupling strength increases in the ODE model. Such variational properties of oscillations depend also on the magnitudes of time delays in delay model. We also illustrate the difference between the dynamics in systems modeled with linear degradation and the ones in systems with Michaelis-Menten type reactions for the degradation. The chief concerns are the connections between the dynamics in these models and the mechanism for the segmentation clocks, and the pertinence of mathematical modeling on somitogenesis in zebrafish.
Assuntos
Relógios Biológicos/genética , Padronização Corporal/genética , Modelos Biológicos , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Animais , Comunicação Celular/genética , Biologia Computacional , Simulação por Computador , Regulação da Expressão Gênica no Desenvolvimento , Cinética , Conceitos Matemáticos , Somitos/embriologia , Somitos/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
BACKGROUND: The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. OBJECTIVES: We sought to characterize the evolutionary patterns of the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. METHODS: We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust. RESULTS: One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kUA/L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. CONCLUSIONS: Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma.
Assuntos
Antígenos de Dermatophagoides/imunologia , Asma/diagnóstico , Imunoglobulina E/metabolismo , Rinite Alérgica/diagnóstico , Adolescente , Adulto , Idade de Início , Animais , Asma/epidemiologia , Asma/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Reações Cruzadas , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Prevalência , Prognóstico , Pyroglyphidae/imunologia , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , Fatores de Risco , Adulto JovemRESUMO
Brain-derived neurotrophic factor (BDNF) is required for the development of the nervous system, proper cognitive function and memory formation. While aberrant expression of BDNF has been implicated in neurological disorders, the transcriptional regulation of BDNF remains to be elucidated. In response to different stimuli, BDNF expression can be initiated from different promoters. Several studies have suggested that the expression of BDNF is regulated by promoter methylation. An emerging theme points to the possibility that histone modifications at the BDNF promoters may link to the neurological pathology. Thus, understanding the epigenetic regulation at the BDNF promoters will shed light on future therapies for neurological disorders. The present review summarizes the current knowledge of histone modifications of the BDNF gene in neuronal diseases, as well as the developmental regulation of the BDNF gene based on data from the Encyclopedia of DNA Elements (ENCODE).
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Doenças Neurodegenerativas/genética , Animais , Histonas/metabolismo , Humanos , Processamento de Proteína Pós-TraducionalAssuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica , Hipersensibilidade/terapia , Adolescente , Adulto , Idoso , Animais , Método Duplo-Cego , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Ragweed pollen allergy is the most common seasonal allergy in western Romania. Prolonged exposure to ragweed pollen may induce sensitization to pan-allergens such as calcium-binding proteins (polcalcins) and progression to more severe symptoms. We aimed to detect IgE sensitization to recombinant Amb a 9 and Amb a 10 in a Romanian population, to assess their potential clinical relevance and cross-reactivity, as well as to investigate the relation with clinical symptoms. rAmb a 9 and rAmb a 10 produced in Escherichia coli were used to detect specific IgE in sera from 87 clinically characterized ragweed-allergic patients in ELISA, for basophil activation experiments and rabbit immunization. Rabbit rAmb a 9- and rAmb a 10-specific sera were used to detect possible cross-reactivity with rArt v 5 and reactivity towards ragweed and mugwort pollen extracts. The results showed an IgE reactivity of 25% to rAmb a 9 and 35% to rAmb a 10. rAmb a 10 induced basophil degranulation in three out of four patients tested. Moreover, polcalcin-negative patients reported significantly more skin symptoms, whereas polcalcin-positive patients tended to report more respiratory symptoms. Furthermore, both rabbit antisera showed low reactivity towards extracts and showed high reactivity to rArt v 5, suggesting strong cross-reactivity. Our study indicated that recombinant ragweed polcalcins might be considered for molecular diagnosis.
Assuntos
Proteínas de Ligação ao Cálcio , Reações Cruzadas , Imunoglobulina E , Rinite Alérgica Sazonal , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Reações Cruzadas/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/sangue , Romênia , Proteínas de Ligação ao Cálcio/imunologia , Antígenos de Plantas/imunologia , Alérgenos/imunologia , Feminino , Masculino , Ambrosia/imunologia , Coelhos , Adulto , Extratos VegetaisRESUMO
Patients with schizophrenia tend to have deficits in emotion recognition (ER) that affect their social function. However, the commonly-used ER measures appear incomprehensive, unreliable and invalid, making it difficult to comprehensively evaluate ER. The purposes of this study were to develop the Computerized Emotion Recognition Video Test (CERVT) evaluating ER ability in patients with schizophrenia. This study was divided into two phases. First, we selected candidate CERVT items/videos of 8 basic emotion domains from a published database. Second, we validated the selected CERVT items using Rasch analysis. Finally, the 269 patients and 177 healthy adults were recruited to ensure the participants had diverse abilities. After the removal of 21 misfit (infit or outfit mean square > 1.4) items and adjustment of the item difficulties of the 26 items with severe differential item functioning, the remaining 217 items were finalized as the CERVT items. All the CERVT items showed good model fits with small eigenvalues (≤ 2) based on the residual-based principal components analysis for each domain, supporting the unidimensionality of these items. The 8 domains of the CERVT had good to excellent reliabilities (average Rasch reliabilities = 0.84-0.93). The CERVT contains items of the 8 basic emotions with individualized scores. Moreover, the CERVT showed acceptable reliability and validity, and the scores were not affected by examinees' gender. Thus, the CERVT has the potential to provide a comprehensive, reliable, valid, and gender-unbiased assessment of ER for patients with schizophrenia.