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1.
Cureus ; 16(4): e57520, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38707094

RESUMO

Background The thoracic ultrasound (TUS) is a monitoring tool that has gained worldwide popularity in various scenarios, offering the opportunity for dynamic, bedside evaluations. Recent studies indicate that the use of TUS enables the diagnosis of pathologies resulting from blunt chest trauma (BCT), yielding favorable outcomes. This study aimed to compare the utility of TUS versus chest radiography (CXR) in diagnosing pulmonary pathologies resulting from closed-chest traumas. Methodology A prospective cross-sectional study was conducted with a sample of 58 patients diagnosed with BCT who sought emergency care at the "Dr. Luis Razetti" University Hospital in Barcelona, Venezuela, from November 2023 to January 2024. Results Of the patients, 75.9% (n = 44) were male, with an average age of 37.8 years (standard deviation = 18.4 years). Injuries were reported in 8.6% (n = 5) of the patients, including 60% (n = 3) pneumothorax and 40% (n = 2) hemothorax. Ultrasound results coincided with CXR in 94.8% (n = 55) of the cases, with a Cohen's kappa coefficient of 0.9 (95% confidence interval (CI) = 0.642-1.0). TUS demonstrated higher sensitivity than CXR (100% vs. 60%) for detecting hemothorax and pneumothorax in patients with BCT, with an area under the receiver operating characteristic curve of 0.991 (95% CI = 0.968-1.013). Conclusions BCT predominantly occurred in young males, resulting primarily in pneumothorax and hemothorax lesions, detectable with higher sensitivity through TUS compared to CXR. The use of TUS should be considered an essential component of the initial assessment for individuals with BCT.

3.
Rev Alerg Mex ; 71(1): 64-65, 2024 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-38683082

RESUMO

OBJECTIVE: To quantify the production of Th1/Th2/Th17 cytokines induced by Ascaris lumbricoides antigens in peripheral blood mononuclear cells (PBMCs) using a multiplex technique. METHODS: PBMCs were cultured from individuals with mild A. lumbricoides infection (n = 20) and uninfected individuals (n = 21) and stimulated with A. lumbricoides extract (ExtAscaris), a mix of anti-CD2/CD3/CD28 (CDmix) as a positive control, and only medium (negative control). Cytokines in the supernatants were measured using the BD™ Cytometric Bead Array Human Th1/Th2/Th17 kit, to identify IFN-γ, TNF, IL-10, IL-6, IL-4, IL-2, and IL-17A. Readings were taken on a spectral cytometer (Northern Lights, Cytek, USA), and analysis was performed using R software with packages "tidyverse," "beadplexr," "flowCore," and "arsenal." Cytokine concentrations were calculated using a 5-parameter logistic curve. The t-test was used to compare cases and controls, and statistical significance was set at p < 0.05. The study was approved by the Ethics Committee of the University of Cartagena and the participants provided informed consent. This study was financially supported by the Colombian Sistema General de Regalías under the BPIN2020000100405 - BPIN2020000100364. RESULTS: Efficient fluorescence intensity extraction for each cytokine was achieved using detection channel R8 and the "mclust" clustering model (Figure 1). No significant differences were found in the levels of the seven cytokines between cases and controls (Figure 2). Although the IFN-γ response to ExtAscaris was higher in cases than in controls (252.5 ng/mL vs. 173.1 ng/mL), the difference was not significant. IL-17A (detection limit: 18.9 pg/mL) was more detectable in cases than controls (5 cases, 23% vs. 2 controls, 9.5%). IL-4 was only detected in the supernatants from CDmix-stimulated cultures but not with the Ascaris extract (Figure 2). CONCLUSIONS: The multiplex technique using spectral flow cytometry combined with open-source software analysis proved applicable for quantifying cytokines induced by A. lumbricoides antigens in PBMCs. However, a more sensitive method is needed to evaluate IL-4 response in the context of ascariasis. The results did not reveal significant differences in cytokine production between cases and controls for the evaluated stimuli.


OBJETIVOS: Cuantificar la producción de citoquinas Th1/Th2/Th17, inducida por antígenos de Ascaris lumbricoides en PBMCs, utilizando una técnica de multiplex. MÉTODOS: Se realizaron cultivos de PBMCs de personas con infección leve por A. lumbricoides (n = 20), y no infectadas (n = 21), y se estimularon con extracto de A. lumbricoides (ExtAscaris), un mix de anti-CD2/CD3/CD28 (CDmix), como control positivo, y solo medio (control negativo). Las citoquinas en los sobrenadantes, se midieron usando el estuche BD™ Cytometric Bead Array Human Th1/Th2/Th17, para identificar IFN-γ, TNF, IL-10, IL-6, IL-4, IL-2 e IL-17A. La lectura se realizó en un citómetro espectral (Northern Lights, Cytek, USA), y el análisis en software R, usando los paquetes tidyverse, beadplexr, flowCore y arsenal. Se calculó la concentración de citoquinas mediante ajuste de curva logística de cinco parámetros. Se empleó la prueba t para comparar casos y controles y una p < 0,05, se consideró como significativa. Se contó con autorización del Comité de Ética de la Universidad de Cartagena para hacer la investigación y con el consentimiento informado por parte de los participantes. Este trabajo fue financiado por el Sistema General de Regalías de Colombia, bajo el BPIN2020000100405 - BPIN2020000100364. RESULTADOS: Al utilizar el canal de detección R8 para identificar las citoquinas y el modelo de agrupamiento mclust, se extrajo eficientemente la intensidad de fluorescencia para cada citoquina (Figura 1). No se encontraron diferencias significativas en los niveles de las siete citoquinas entre casos y controles (Figura 2). Aunque la respuesta de IFN-, γ hacia ExtAscaris fue más alta en los casos de controles (252,5 ng/mL vs 173,1 ng/mL), la diferencia no fue significativa. La IL-17A (límite de detección: 18,9 pg/mL) fue más detectable en casos que en controles (cinco casos, 23% vs dos controles, 9,5%). La IL-4 solo se detectó en los sobrenadantes de cultivos estimulados con CDmix, pero no con el extracto de Ascaris (Figura 2). CONCLUSIONES: La técnica multiplex por citometría espectral, combinada con el análisis en software de licencia libre, se mostró aplicable para cuantificar citoquinas inducidas por antígenos de A. lumbricoides en PBMCs. Sin embargo, se requiere de un método más sensible para evaluar la respuesta de IL-4 en el contexto de la ascariasis. Los resultados no revelaron diferencias significativas en la producción de citoquinas entre casos y controles para los estímulos evaluados.


Assuntos
Ascaríase , Citocinas , Citometria de Fluxo , Humanos , Citocinas/sangue , Citometria de Fluxo/métodos , Ascaríase/imunologia , Ascaríase/diagnóstico , Masculino , Feminino , Adulto , Animais , Leucócitos Mononucleares/imunologia , Ascaris lumbricoides/imunologia , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Antígenos de Helmintos/imunologia
4.
Rev Alerg Mex ; 71(1): 69, 2024 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-38683086

RESUMO

OBJECTIVE: To compare the relative frequencies of immune cell populations in the peripheral blood according to A. lumbricoides infection status. METHODS: Peripheral blood samples were collected from participants infected (n = 35) and uninfected with A. lumbricoides (n=27) residing in different rural municipalities of Bolívar. Infection was diagnosed using two coprological examinations and the Kato-Katz technique. Immunophenotyping was performed using two panels of markers and staining in fresh blood. The flow cytometry reading was performed on a spectral cytometer (Northern Lights, Cytek, USA). The populations identified in the first panel (Figure 1) were T lymphocytes (CD45+ CD3+), CD4+ or CD8+, B lymphocytes (CD45+ SSClow CD3- CD19+), neutrophils (CD45+ SSChi CD3- CD16+), and eosinophils (CD45+ SSChi CD3- CD16low). Monocytes were identified in another panel (Figure 2): classical (CD14++ CD16 -), intermediate (CD14++ CD16+), and non-classical (CD14+ CD16++). Dendritic cells, including CD123 + + CD303 + (plasmacytoid), HLA-DR + + CD1c + (myeloid CD1c +), and CD14-CD141 + + (myeloid CD141 +), were also identified. The study received approval from the Ethics Committee of the University of Cartagena, and participants provided informed consent. Funding was provided by the Colombian Sistema General de Regalías under BPIN2020000100405 - BPIN2020000100364. RESULTS: No significant differences were observed in age [mean cases: 35.69 (SD: 17.7) vs. controls: 37.04 (SD: 15.6) years] or sex (cases: 62.9% vs. controls: 74.1%) (Table 1). All infections were mild, with a median of 96 eggs (IQR, 48-216). A marginally significant difference was observed only in the percentage of neutrophils (45.37% in cases vs. 54.79% in controls, p=0.041) (Figure 3). Although the frequency of eosinophils was higher in the cases (8.1% vs. 6%), this difference was not significant (p=0.138) (Figure 3). No significant differences were observed in the populations of monocytes or dendritic cells between cases and controls (Figure 4). CONCLUSION: Mild A. lumbricoides infection appears to affect the number of neutrophils in peripheral blood. The low infection intensity in the studied samples may explain the lack of a significant impact on other cellular populations.


OBJETIVO: Comparar las frecuencias relativas de poblaciones de células inmunes en sangre periférica de acuerdo con el estado de infección por A. lumbricoides. MÉTODOS: Se recolectaron muestras de sangre periférica de participantes infectados (n=35) y no infectados con A. lumbricoides (n=27), residentes en distintos municipios rurales de Bolívar. La infección se diagnosticó por dos métodos coprológicos y la técnica de Kato-Katz. El inmunofenotipo se determinó con dos baterías de marcadores y tinciones en sangre fresca. La lectura fue realizada en un citómetro espectral (Northern Lights, Cytek, USA). Las poblaciones identificadas en la primera batería (Figura 1) fueron linfocitos T (CD45+ CD3+) CD4+ o CD8+, linfocitos B (CD45+ SSClow CD3- CD19+), neutrófilos (CD45+ SSChi CD3- CD16+), y eosinófilos (CD45+ SSChi CD3- CD16low). Los monocitos se identificaron en otra batería (Figura 2): clásicos (CD14++ CD16­), intermedios (CD14++ CD16+), y no clásicos (CD14+ CD16++). También se identificaron células dendríticas, tales como: CD123++ CD303+ (plasmocitoides), HLA-DR++ CD1c+ (mieloides CD1c+), y CD14- CD141++ (mieloides CD141+). El estudio recibió la aprobación del Comité de Ética de la Universidad de Cartagena, y los participantes otorgaron su consentimiento informado. La financiación fue proporcionada por el Sistema General de Regalías de Colombia, bajo el BPIN2020000100405 - BPIN2020000100364. RESULTADOS: No se observaron diferencias significativas en edad [media = casos: 35,69 (DE: 17,7) vs controles: 37,04 (DE: 15,6 años] o sexo (casos: 62,9% vs. controles: 74,1%). Todas las infecciones fueron leves con una mediana de huevos de 96 (RIC: 48 - 216). Solo se encontró diferencia significativa marginal en el porcentaje de neutrófilos (45,37% en los casos vs 54,79% en controles, p=0,041). Si bien la frecuencia de eosinófilos fue más alta en los casos (8,1% vs. 6%), esta diferencia no alcanzó la significancia (p=0,138). No se observaron diferencias significativas en las poblaciones de monocitos o células dendríticas entre casos y controles (Figura 4). CONCLUSIÓN: La infección leve por A. lumbricoides parece afectar el número de neutrófilos en sangre periférica. Es posible que por la baja intensidad de la infección en la muestra estudiada, no se detecte un impacto importante de la misma sobre el resto de las poblaciones celulares. Palabras claves: Helmintos; Ascaris lumbricoides; Citometría de flujo; Inmunofenotipado; Neutrófilos.


Assuntos
Ascaríase , Humanos , Masculino , Feminino , Ascaríase/imunologia , Ascaríase/epidemiologia , Adulto , Adolescente , Animais , Adulto Jovem , Saúde da População Rural , Criança , Ascaris lumbricoides , Pessoa de Meia-Idade , Colômbia
5.
Rev Alerg Mex ; 71(1): 74, 2024 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-38683091

RESUMO

OBJECTIVE: Determine the main asthma phenotypes in a population of asthmatic children in Cartagena, Colombia. METHODS: 107 children (7 to 17 years old) with a previous diagnosis of asthma were recruited. Biomarkers of T2 inflammation were evaluated by measuring FeNO, eosinophil count in peripheral blood by hemocytometry, and determination of specific IgE to mite allergens by ELISA. The study was approved by the ethics committee of the University of Cartagena (SGR, Grant BPIN2020000100405). RESULTS: The average age of patients was 10,9 years. 19,6% of the children did not show elevation of any of the T2 inflammation biomarkers evaluated (FeNO<20ppb, eos<300/ul, negative specific IgE), so they were considered patients with non-allergic asthma (non-T2). 71,9% of all patients were sensitized to at least one allergen, this phenotype was considered allergic asthma. 30,8% of the patients presented the three elevated biomarkers (FeNO>20ppb + eos >300/ul + positive specific IgE), this phenotype was classified as high T2 allergic asthma. A moderate correlation (Spearman rho=0,44, p<0,0001) was found between FeNO values and eosinophil counts. CONCLUSION: In this study, the following phenotypes were found: allergic asthma, high T2 asthma, and non-allergic asthma. Most patients presented a type 2 inflammatory phenotype with allergic sensitization. In addition to the measurement of specific IgE, the use of FeNO and eosinophil count in peripheral blood help to accurately determine those patients with high T2 asthma phenotypes.


OBJETIVO: Determinar los fenotipos principales de asma en una población de niños asmáticos en Cartagena, Colombia. MÉTODOS: Se reclutaron 107 niños (entre 7 y 17 años), con diagnóstico previo de asma. Se evaluaron biomarcadores de inflamación T2 mediante la medición de FeNO, conteo de eosinófilos en sangre periférica mediante hemocitometría, y la determinación de IgE específica a alergenos de ácaros mediante ELISA. El estudio fue aprobado por el Comité de Ëtica de la Universidad de Cartagena (SGR, Grant BPIN2020000100405). RESULTADOS: La edad media de los pacientes fue de 10,9 años. El 19,6% de los niños no mostró elevación de ninguno de los biomarcadores de inflamación T2 evaluados (FeNO<20 ppb, eos<300/ul, IgE específica negativa), por lo que se consideraron como pacientes con asma no alérgica (no-T2). El 71,9% de todos los pacientes estaban sensibilizados al menos a un alergeno considerándose este fenotipo como asma alérgica. El 30,8% de los pacientes presentaron los tres biomarcadores elevados (FeNO>20 ppb + eos >300/ul + IgE específica positiva), clasificando este fenotipo como asma alérgica T2 alta. Se encontró una correlación moderada (Spearman rho=0,44, p<0,0001) entre los valores de FeNO y los conteos de eosinófilos. CONCLUSIÓN: En este estudio se encontraron los siguientes fenotipos de asma alérgica: asma T2 alta y asma no alérgica. La mayoría de los pacientes presentó un fenotipo inflamatorio tipo 2 con sensibilización alérgica. Además de la medición de la IgE específica, el uso del FeNO y los conteos de eosinófilos en sangre periférica ayudan a determinar con mayor exactitud a aquellos pacientes con fenotipos de asma T2 alto.


Assuntos
Asma , Fenótipo , Humanos , Asma/sangue , Criança , Adolescente , Masculino , Feminino , Imunoglobulina E/sangue , Eosinófilos , Clima Tropical , Biomarcadores/sangue , Colômbia , Contagem de Leucócitos
6.
Front Immunol ; 15: 1328401, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481989

RESUMO

Background: Ascaris lumbricoides cystatin (Al-CPI) prevents the development of allergic airway inflammation and dextran-induced colitis in mice models. It has been suggested that helminth-derived cystatins inhibit cathepsins in dendritic cells (DC), but their immunomodulatory mechanisms are unclear. We aimed to analyze the transcriptional profile of human monocyte-derived DC (moDC) upon stimulation with Al-CPI to elucidate target genes and pathways of parasite immunomodulation. Methods: moDC were generated from peripheral blood monocytes from six healthy human donors of Denmark, stimulated with 1 µM of Al-CPI, and cultured for 5 hours at 37°C. RNA was sequenced using TrueSeq RNA libraries and the NextSeq 550 v2.5 (75 cycles) sequencing kit (Illumina, Inc). After QC, reads were aligned to the human GRCh38 genome using Spliced Transcripts Alignment to a Reference (STAR) software. Differential expression was calculated by DESEq2 and expressed in fold changes (FC). Cell surface markers and cytokine production by moDC were evaluated by flow cytometry. Results: Compared to unstimulated cells, Al-CPI stimulated moDC showed differential expression of 444 transcripts (|FC| ≥1.3). The top significant differences were in Kruppel-like factor 10 (KLF10, FC 3.3, PBH = 3 x 10-136), palladin (FC 2, PBH = 3 x 10-41), and the low-density lipoprotein receptor (LDLR, FC 2.6, PBH = 5 x 10-41). Upregulated genes were enriched in regulation of cholesterol biosynthesis by sterol regulatory element-binding proteins (SREBP) signaling pathways and immune pathways. Several genes in the cholesterol biosynthetic pathway showed significantly increased expression upon Al-CPI stimulation, even in the presence of lipopolysaccharide (LPS). Regarding the pathway of negative regulation of immune response, we found a significant decrease in the cell surface expression of CD86, HLA-DR, and PD-L1 upon stimulation with 1 µM Al-CPI. Conclusion: Al-CPI modifies the transcriptome of moDC, increasing several transcripts encoding enzymes involved in cholesterol biosynthesis and SREBP signaling. Moreover, Al-CPI target several transcripts in the TNF-alpha signaling pathway influencing cytokine release by moDC. In addition, mRNA levels of genes encoding KLF10 and other members of the TGF beta and the IL-10 families were also modified by Al-CPI stimulation. The regulation of the mevalonate pathway and cholesterol biosynthesis suggests new mechanisms involved in DC responses to helminth immunomodulatory molecules.


Assuntos
Cistatinas , Monócitos , Humanos , Animais , Camundongos , Ascaris lumbricoides , Ácido Mevalônico/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Diferenciação Celular , Citocinas/metabolismo , Inflamação/metabolismo , Imunidade , Células Dendríticas , RNA/metabolismo
7.
Biology (Basel) ; 12(10)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37887050

RESUMO

Immunity to Ascaris lumbricoides influences the pathogenesis of allergic diseases. Antibody responses to its proteins have been found to be associated with asthma presentation; however, helminth products that induce immunosuppression have been reported, which also raise specific antibodies. We aimed to evaluate antibody responses (IgE, IgG4 and IgG) to two A. lumbricoides molecules, Asc l 5 and Al-CPI (an anti-inflammatory Cysteine Protease Inhibitor), in an endemic population, exploring their relationships with the infection and asthma. The two molecules were produced as recombinant proteins in E. coli expression systems. Specific antibodies were detected by ELISA. Lower human IgE, but higher IgG4 and IgG antibody levels were observed for Al-CPI than for rAsc l 5. The IgE/IgG4 isotype ratio was significantly higher for Asc l 5 than for Al-CPI. In humans Al-CPI did not induce basophil activation as has been previously described for Asc l 5. In mice, Al-CPI induced fewer IgE responses, but more IgG2a antibody titers than rAsc l 5. Our results suggest that these molecules elicit different patterns of immune response to A. lumbricoides.

8.
Curr Allergy Asthma Rep ; 23(7): 363-373, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37269427

RESUMO

PURPOSE OF REVIEW: Helminth infections modify the natural history of allergic diseases, by either decreasing or increasing their symptoms. Several helminth components are involved in the increasing of the allergic response and symptoms, overcoming the concomitant immunosuppression of helminthiases. However, the role of individual IgE-binding molecules in this process remains to be defined. RECENT FINDINGS: We updated the list of helminth allergens and IgE-binding molecules, their effects on asthma presentation, and their impact on allergy diagnosis. Data from genetic and epigenetic studies of ascariasis are analyzed. A new species-specific A. lumbricoides allergen has been discovered, with potential use in molecular diagnosis. Most helminth IgE-binding components are not officially classified as allergens in the WHO/IUIS database, although there is evidence of their influence increasing allergic manifestations. Further immunological characterization of these components is needed to better understand their mechanisms of action and evaluate the ways in which they can influence the diagnosis of allergy.


Assuntos
Asma , Hipersensibilidade , Parasitos , Animais , Humanos , Alérgenos , Imunoglobulina E , Hipersensibilidade/diagnóstico , Asma/diagnóstico
9.
Int J Mol Sci ; 24(6)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36982614

RESUMO

Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a Blomia tropicalis allergen. Blo t 2 was produced as a recombinant protein in Escherichia coli. Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.


Assuntos
Alérgenos , Pyroglyphidae , Humanos , Camundongos , Animais , Dermatophagoides pteronyssinus , Imunoglobulina E , Inflamação , Antígenos de Dermatophagoides
10.
Clin Exp Allergy ; 53(8): 821-832, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36779555

RESUMO

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.


Assuntos
Hipersensibilidade , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Hipersensibilidade/terapia , Alérgenos , Inflamação , Citocinas , Dessensibilização Imunológica , Imunoglobulina E
11.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362143

RESUMO

Humans have coexisted with helminths and bacteria for the entire existence of our species. Nowadays, helminth infections affect more than 1.9 billion people worldwide, especially in underdeveloped regions that lack optimal sanitary conditions. In addition, commensal microorganisms inhabit several compartments of humans, including the gastrointestinal tract, constituting what we know as the microbiota. Helminths and bacterial microbiota can interact in various ways. In this review, the interactions between helminths and commensal bacteria are analyzed in both animal models and humans. In developing countries, the gut microbiota exhibits high diversity, which could be linked to the high burden of helminthiasis in these areas. In fact, several studies show that helminth infections are associated with an increased gut microbiota diversity and changes in its composition. Interestingly, these changes can modify the risk for some diseases, such as asthma, colitis, viral infections, and metabolic conditions. Besides, the microbiota is necessary for the establishment of some helminth infections and can also influence the evolution of these diseases. Specific bacterial taxa can contribute to the resistance or susceptibility to certain helminths. The mechanisms underlying helminth-microbiota interactions are not completely understood. More research is necessary to address this and other unmet needs, especially considering that available studies are heterogeneous and sometimes yield conflicting results.


Assuntos
Helmintíase , Helmintos , Microbiota , Humanos , Animais , Amigos , Helmintíase/parasitologia , Bactérias
12.
World Allergy Organ J ; 15(9): 100686, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35966894

RESUMO

An outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started in Wuhan, Hubei Province, China and quickly spread around the world. Current evidence is contradictory on the association of asthma with COVID-19 and associated severe outcomes. Type 2 inflammation may reduce the risk for severe COVID-19. Whether asthma diagnosis may be a risk factor for severe COVID-19, especially for those with severe disease or non-allergic phenotypes, deserves further attention and clarification. In addition, COVID-19 does not appear to provoke asthma exacerbations, and asthma therapeutics should be continued for patients with exposure to COVID-19. Changes in the intensity of pollinization, an earlier start and extension of the pollinating season, and the increase in production and allergenicity of pollen are known direct effects that air pollution has on physical, chemical, and biological properties of the pollen grains. They are influenced and triggered by meteorological variables that could partially explain the effect on COVID-19. SARS-CoV-2 is capable of persisting in the environment and can be transported by bioaerosols which can further influence its transmission rate and seasonality. The COVID-19 pandemic has changed the behavior of adults and children globally. A general trend during the pandemic has been human isolation indoors due to school lockdowns and loss of job or implementation of virtual work at home. A consequence of this behavior change would presumably be changes in indoor allergen exposures and reduction of inhaled outdoor allergens. Therefore, lockdowns during the pandemic might have improved some specific allergies, while worsening others, depending on the housing conditions.

13.
Allergy ; 77(5): 1534-1544, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34695231

RESUMO

BACKGROUND: The shrimp Litopenaeus vannamei is an important source of food allergens but its allergenic repertoire is poorly characterized. Cross-reactivity between crustacean and mites has been reported, with tropomyosin, the most relevant allergen involved. The aim of this study was to investigate the structural and immunological properties of a recombinant Fatty Acid Binding Protein (FABP) family from L. vannamei (LvFABP). METHODS: ELISA, skin prick test (SPT) and basophil activation assays were performed to determine IgE reactivity and allergenic activity of LvFABP. LC-MS/MS and Circular Dichroism experiments were done for structural analysis. B-cell epitope mapping with overlapping peptides, and cross-inhibition studies using human sera were done to identify antigenic regions and cross-reactivity. RESULTS: The recombinant LvFABP bound serum IgE from 27% of 36 shrimp allergic patients and showed allergenic activity when tested for basophil activation and SPT in a selected number of them. CD-spectroscopy of LvFABP revealed that the protein is folded with a secondary structure composed of mainly ß-strands and a smaller fraction of α helices. This is consistent with molecular modelling results, which exhibit a typical ß barrel fold with two α-helices and ten ß-strands. Epitope mapping identified two IgE-binding antigenic regions and inhibition assays found high cross-reactivity between LvFABP and Blo t 13, mediated by the antigenic region involving amino acids 54 to 72. CONCLUSIONS: Our results show that LvFABP is a shrimp allergen that cross reacts with the house dust mite allergen Blo t 13 and has allergenic activity, which suggest that it could be clinically relevant in case of shellfish allergy. This new allergen, named Lit v 13, will also help to understand basic mechanisms of sensitization to shrimp.


Assuntos
Hipersensibilidade Alimentar , Penaeidae , Alérgenos , Animais , Cromatografia Líquida , Reações Cruzadas , Proteínas de Ligação a Ácido Graxo , Hipersensibilidade Alimentar/diagnóstico , Humanos , Imunoglobulina E , Espectrometria de Massas em Tandem
14.
Front Immunol ; 12: 678661, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335580

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators. Methods: Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the "COVID-19 Drug and Gene Set Library" and with experimentally tested protein biomarkers of severe COVID-19. Results: Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19. Conclusions: COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.


Assuntos
Asma/imunologia , COVID-19/imunologia , Mediadores da Inflamação/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , SARS-CoV-2/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/diagnóstico , Biomarcadores/sangue , COVID-19/diagnóstico , Quimiocina CXCL9/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Índice de Gravidade de Doença , Regulação para Cima
15.
Infect Genet Evol ; 94: 104997, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252615

RESUMO

BACKGROUND: The systematics and taxonomy of Ascaris lumbricoides and Ascaris suum, two of the world's most widespread nematodes, still represent a highly debated scientific issue. Two different transmission scenarios have been described according to endemicity: separated host-specific transmission cycles in endemic regions, and a single pool of infection shared by humans and pigs in non-endemic regions. The swine roundworm A. suum is now recognized as an important cause of human ascariasis also in endemic areas such as China, where cross-infections and hybridization have also been reported, as well as in non-endemic regions like Italy. This study aimed to investigate the molecular epidemiology of human and pig ascariasis in three countries representing different epidemiological scenarios: Italy as a non-endemic country, Colombia as an endemic country, and Slovakia as a non-endemic country, but with a poor socio-economic context linked to some focal populations of Roma settlements. MATERIALS AND METHODS: A total of 237 nematodes were analysed: 46 from Colombia (13 from humans, 33 from pigs), 114 from Slovakia (20 from humans, 94 from pigs) and 77 from Italy (17 from humans and 60 from pigs). Genotyping by PCR-RFLP of nuclear (ITS) and sequencing of mitochondrial (cox1) target regions were performed. ITS genotypes were used to estimate the Hardy-Weinberg (HW) equilibrium according to hosts and country of origin. The partial cox1 sequences were used to analyse genetic polymorphisms according to hosts and country of origin, as well as to infer the network of haplotypes, their evolutionary relationships and geographical distribution. RESULTS: 110 quality cox1 sequences were obtained. Haplotype network revealed three main groups corresponding to clade A, B and C. Clade C included most of the human cases from Italy, while those from Slovakia and Colombia were grouped in clade B. Ascaris from Italian and Colombian pigs showed HW equilibrium at the ITS marker, while disequilibrium was found in A. lumbricoides from Slovak pigs, which suggest a high unexpected amount of roundworms of human origin circulating also in pigs. CONCLUSIONS: This study updates and extends the current understanding of Ascaris species and genotypes circulating in different epidemiological scenarios, with particular attention to the inclusion of human-derived Ascaris in the phylogenetic cluster C. Despite the evidence of HW equilibrium in the ITS in pig-derived Italian samples, the amount of genetic variation seems to support the existence of two closely related species.


Assuntos
Ascaríase/veterinária , Ascaris lumbricoides/genética , Ascaris suum/genética , Genótipo , Doenças dos Suínos/parasitologia , Animais , Ascaríase/parasitologia , Colômbia , Itália , Eslováquia , Sus scrofa , Suínos
17.
Nutrients ; 13(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668787

RESUMO

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.


Assuntos
Epigênese Genética/imunologia , Hipersensibilidade , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Materna , Feminino , Humanos , Recém-Nascido , Gravidez
18.
Parasitology ; : 1-13, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33563346

RESUMO

Helminth infections such as ascariasis elicit a type 2 immune response resembling that involved in allergic inflammation, but differing to allergy, they are also accompanied with strong immunomodulation. This has stimulated an increasing number of investigations, not only to better understand the mechanisms of allergy and helminth immunity but to find parasite-derived anti-inflammatory products that could improve the current treatments of chronic non-communicable inflammatory diseases such as asthma. A great number of helminth-derived immunomodulators have been discovered and some of them extensively analysed, showing their potential use as anti-inflammatory drugs in clinical settings. Since Ascaris lumbricoides is one of the most successful parasites, several groups have focused on the immunomodulatory properties of this helminth. As a result, several excretory/secretory components and purified molecules have been analysed, revealing interesting anti-inflammatory activities potentially useful as therapeutic tools. One of these molecules is A. lumbricoides cystatin, whose genomic, cellular, molecular, and immunomodulatory properties are described in this review.

19.
World Allergy Organ J ; 14(2): 100515, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33552380

RESUMO

BACKGROUND: The COVID-19 outbreak brought an unprecedented challenge to the world. Knowledge in the field has been increasing exponentially and the main allergy societies have produced guidance documents for better management of allergic patients during this period. However, few publications so far have provided real-life data from the allergy community concerning allergy practice during the COVID-19 outbreak. Therefore, we proposed an international survey on the management of allergic patients during the current pandemic. METHODS: We performed an online survey undertaken to reach out the worldwide allergy community by e-mail and social media. The web-based questionnaire contained 24 questions covering demographic data from the participants, clinical practice during this period, and questions related to the new international classification and coding tools addressed for COVID-19. It was circulated for 8 weeks and had anonymous and volunteer context. RESULTS: Data are presented for 635 participants from 78 countries of all continents. Allergists with long-term professional experience were the main audience. As expected, we received many responses as "I have no data" or "I don't know" to the questions of the survey. However, most with more experience on managing allergic patients during the pandemic agreed that patients suffering from allergic or hypersensitivity conditions have no increased risk of contracting COVID-19 or developing SARS CoV-2. Also, participants mentioned that none of the allergy treatments (inhaled corticosteroids, allergen immunotherapy, biological agents) increased the risk of contracting COVID-19 infection including severe presentations. CONCLUSION: The data presented are a starting point in the process of getting feedback on all the recommendations provided by the allergy societies; it could also be the basis of new strategies to support health professionals while new COVID-19 specific treatments and vaccines are being explored. The information here presented intends to be helpful to the community but represents a course of action in a highly specific situation due to the state of emergency, and it should be helpful to health systems.

20.
World Allergy Organ J ; 14(1): 100499, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33510831

RESUMO

Indoor environments contribute significantly to total human exposure to air pollutants, as people spend most of their time indoors. Household air pollution (HAP) resulting from cooking with polluting ("dirty") fuels, which include coal, kerosene, and biomass (wood, charcoal, crop residues, and animal manure) is a global environmental health problem. Indoor pollutants are gases, particulates, toxins, and microorganisms among others, that can have an impact especially on the health of children and adults through a combination of different mechanisms on oxidative stress and gene activation, epigenetic, cellular, and immunological systems. Air pollution is a major risk factor and contributor to morbidity and mortality from major chronic diseases. Children are significantly affected by the impact of the environment due to biological immaturity, prenatal and postnatal lung development. Poor air quality has been related to an increased prevalence of clinical manifestations of allergic asthma and rhinitis. Health professionals should increase their role in managing the exposure of children and adults to air pollution with better methods of care, prevention, and collective action. Interventions to reduce household pollutants may promote health and can be achieved with education, community, and health professional involvement.

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