Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
Mais filtros

Bases de dados
Tipo de documento
Intervalo de ano de publicação
1.
Kidney Int ; 106(2): 302-316, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38692408

RESUMO

Organ shortage is a major challenge in kidney transplantation but the use of older donors, often with co-morbidities, is hampered by inconsistent outcomes. Methods of accurately stratifying marginal donor organs by clinical and histological assessment are lacking. To better understand organ variability, we profiled the transcriptomes of 271 kidneys from deceased donors at retrieval. Following correction for biopsy composition, we assessed molecular pathways that associated with delayed, and sub-optimal one-year graft function. Analysis of cortical biopsies identified an adaptive immune gene-rich module that significantly associated with increasing age and worse outcomes. Cellular deconvolution using human kidney reference single cell transcriptomes confirmed an increase in kidney-specific B and T cell signatures, as well as kidney macrophage, myofibroblast and fibroblast gene sets in this module. Surprisingly, innate immune pathway and neutrophil gene signature enrichment was associated with better outcomes. Thus, our work uncovers cellular molecular features of pathological organ ageing, identifiable at kidney retrieval, with translational potential.


Assuntos
Perfilação da Expressão Gênica , Transplante de Rim , Rim , Transcriptoma , Humanos , Transplante de Rim/efeitos adversos , Rim/patologia , Rim/imunologia , Biópsia , Pessoa de Meia-Idade , Masculino , Adulto , Feminino , Perfilação da Expressão Gênica/métodos , Idoso , Fatores Etários , Doadores de Tecidos , Envelhecimento/patologia , Envelhecimento/genética , Envelhecimento/imunologia , Patologia Molecular/métodos , Imunidade Inata , Imunidade Adaptativa/genética , Adulto Jovem , Análise de Célula Única , Sobrevivência de Enxerto/imunologia
2.
Gene Ther ; 31(5-6): 273-284, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38355967

RESUMO

Adeno-associated virus (AAV) based gene therapy has demonstrated effective disease control in hemophilia. However, pre-existing immunity from wild-type AAV exposure impacts gene therapy eligibility. The aim of this multicenter epidemiologic study was to determine the prevalence and persistence of preexisting immunity against AAV2, AAV5, and AAV8, in adult participants with hemophilia A or B. Blood samples were collected at baseline and annually for ≤3 years at trial sites in Austria, France, Germany, Italy, Spain, and the United States. At baseline, AAV8, AAV2, and AAV5 neutralizing antibodies (NAbs) were present in 46.9%, 53.1%, and 53.4% of participants, respectively; these values remained stable at Years 1 and 2. Co-prevalence of NAbs to at least two serotypes and all three serotypes was present at baseline for ~40% and 38.2% of participants, respectively. For each serotype, ~10% of participants who tested negative for NAbs at baseline were seropositive at Year 1. At baseline, 38.3% of participants had detectable cell mediated immunity by ELISpot, although no correlations were observed with the humoral response. In conclusion, participants with hemophilia may have significant preexisting immunity to AAV capsids. Insights from this study may assist in understanding capsid-based immunity trends in participants considering AAV vector-based gene therapy.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Dependovirus , Terapia Genética , Hemofilia A , Humanos , Dependovirus/imunologia , Dependovirus/genética , Masculino , Hemofilia A/imunologia , Hemofilia A/terapia , Adulto , Estudos Longitudinais , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Terapia Genética/métodos , Imunidade Adaptativa , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Vetores Genéticos/imunologia , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
3.
Immunohorizons ; 8(1): 106-113, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38252037

RESUMO

Immunology is inherently interdisciplinary. Understanding how the immune system functions requires knowledge from several scientific disciplines, including molecular biology, cellular biology, genetics, and biochemistry. Furthermore, immunology is conceptually complex, requiring the identification of a plethora of immune components and mastery of a large volume of new vocabulary. These attributes can pose challenges to student learning in the undergraduate immunology classroom. Team-based learning (TBL) is a pedagogical method used to increase student engagement in learning, improve student collaboration, and develop communication skills. In a variety of educational settings, TBL activities have been shown to foster a deeper understanding of complex topics, increase student confidence in course content, and improve learning outcomes. In this study, we examined differences in the impact of traditional lecture versus TBL activities on student learning outcomes for four different topics presented in an undergraduate adaptive immunity course composed largely of academically high-performing students. We matched content across two student cohorts, delivered via team-based learning methodology (T cell development and Ab-mediated functions) and traditional lecture (B cell development and T cell effector functions). Student learning was assessed using content questions across a range of Bloom's taxonomy levels, which demonstrated that the TBL activities did not improve examination performance over lecture-based learning in this course. However, students found this learning tool to be valuable, indicating that the TBL activities assisted with preparation for examinations and provided a necessary opportunity to address misconceptions.


Assuntos
Imunidade Adaptativa , Estudantes , Humanos , Diferenciação Celular , Ativação Linfocitária
4.
World J Gastroenterol ; 29(32): 4831-4850, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37701135

RESUMO

Non-alcoholic fatty liver disease (NAFLD) causes significant global disease burden and is a leading cause of mortality. NAFLD induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of NAFLD is widely recognised, the precise triggers for disease progression are still to be fully elucidated. Furthermore, the propagation to cirrhosis is poorly understood. Whilst some progress in terms of treatment options have been explored, an incomplete understanding of the hepatic cellular and molecular alterations limits their clinical utility. We have therefore reviewed some of the key pathways responsible for the pathogenesis of NAFLD such as innate and adaptative immunity, lipotoxicity and fibrogenesis, and highlighted current trials and treatment options for NAFLD patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Imunidade Adaptativa , Progressão da Doença , Carga Global da Doença , Hepatócitos
5.
Front Immunol ; 14: 1108895, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006253

RESUMO

Background: Eosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers. Methods: Blood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE. Results: French children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets. Conclusions: Our study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort.


Assuntos
Esofagite Eosinofílica , Humanos , Criança , Multiômica , Citocinas/metabolismo , Imunidade Adaptativa , Biomarcadores
6.
Vopr Pitan ; 92(1): 6-15, 2023.
Artigo em Russo | MEDLINE | ID: mdl-36883535

RESUMO

Restoring the adaptive potential of an athlete is of paramount importance not only for the implementation of his training and competitive activities, but also for maintaining health. One of the leading place in complex recovery programs in sports is given to full-fledged optimal nutrition, which provides for meeting the body's requirements not only in energy, macro- and micronutrients, but also in minor bioactive compounds. The use of anthocyanin-containing products is a promising strategy for the normalization of metabolic and immune disorders that develop as a result of intense physical and neuro-emotional stress not only in athletes, but also in other groups of people exposed to these factors, including military personnel undergoing training in conditions close to combat. This determines the relevance of this study. The aim of the research was to study the effect of an anthocyanin-enriched diet on hematological profile and cellular immunity in rats after intense physical activity. Material and methods. The experiment was carried out for 4 weeks on 4 groups of male Wistar rats with an initial body weight of ~300 g. The motor activity of the animals of the 1st (control) and 2nd groups was limited by the standard keeping animals in the vivarium, while physically active rats of the 3rd and 4th groups received additional physical activity - training on a treadmill. Before the end of the experiment, the animals of 3rd and 4th groups were given debilitating physical activity on a treadmill (until the rats refused to continue the exercise). Rats of all 4 groups received a standard semi-synthetic diet, water ad libitum. Animals in 2nd and 4th groups were additionally fed blueberry and blackcurrant extract (30% anthocyanins) as part of the diet at a daily dose of 15 mg anthocyanins/kg body weight. Hematological parameters were determined on a Coulter ACT TM 5 diff OV hematological analyzer. Expression of CD45R, CD3, CD4, CD8a, CD161 receptors on rat peripheral blood lymphocytes was determined by direct immunofluorescent staining of whole blood cells using a panel of monoclonal antibodies conjugated with fluorescent dyes: APC, FITC, PE. The measurements were carried out on an FC-500 flow cytometer. Results. Intense physical activity in rats of the 3rd group did not lead to a significant change in erythrocyte parameters compared with the control group. Enrichment of the diet with blueberry and black currant extract (the 2nd and the 4th groups) provided a significant (p<0.05) increase in blood content of hemoglobin (Hb) (150.7±0.9 and 154.4±2.0 vs 145.4±0.9 g/l in control), hematocrit (44.95±0.21 and 46.18±0.64 vs 43.78±0.32%) and the average content of Hb in erythrocytes (18.00±0.20 and 18.03±0.24 vs 17.35±0.24 pg). The absolute content of leukocytes and other cellular elements of the leukocyte formula, as well as leukocyte indices in rats of the experimental groups didn't significantly differ from those of the control rats, which confirms the absence of an inflammatory process. Intense physical activity and anthocyanin enrichment of the diet didn't have a significant effect on rat platelet parameters. Enrichment of the diet of rats of the 4th group with blueberry and black currant extract led to the activation of cellular immunity, as evidenced by a significant (p<0.01) increase in the percentage (from the total content of T-lymphocytes) of T-helpers (70.13 ±1.34 vs 63.75±0.99%) and a decrease in the relative content of cytotoxic T-lymphocytes (28.65±1.38 vs 34.71±0.95%) in comparison with those in rats of the 3rd group and at the level of the trend (р<0.1) - from the 1st group indexes (66.87±1.20 and 31.87±1.26%, accordingly). Intense physical activity led to a decrease in immunoregulatory index in rats of the 3rd group (1.86±0.07) compared with the control (2.13±0.12) (p<0.1), and in animals of the 4th group this indicator was significantly higher (2.50±0.14, p<0.05). In animals of the 3rd group a statistically significant (p<0.05) decrease in the relative content of NK cells in peripheral blood was found compared to the control. Enrichment of the diet of physically active rats with blueberry and black currant extract led to a significant (p<0.05) increase in the percentage of NK cells compared to this indicator in rats of the 3rd group (4.87±0.75 vs 2.08±0.18%) and had no significant difference with the indicator in rats of the control group (4.32±0.98%). Conclusion. The enrichment of the rats' diet with blueberry and blackcurrant extract containing a daily dose of 15 mg of anthocyanins per kg of body weight provides an increase in blood Hb content, hematocrit and the average content Hb in erythrocytes. It has been established that intense physical activity induces the cellular immunity suppression. The activating effect of anthocyanins on adaptive cellular immunity and NK cells, which are lymphocytes of innate immunity, was revealed. The data obtained indicate the effectiveness of the use of bioactive compounds (anthocyanins) to increase the adaptive potential of the organism.


Assuntos
Adaptação Fisiológica , Antocianinas , Condicionamento Físico Animal , Animais , Masculino , Ratos , Antocianinas/administração & dosagem , Eritrócitos , Leucócitos , Ratos Wistar , Imunidade Celular , Imunidade Adaptativa , Dieta
7.
PLoS Comput Biol ; 17(8): e1009209, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34343169

RESUMO

Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. Such modularity improves computational performance and versatility and facilitates data integration. We validated our technology by reproducing known experimental results, including differentiation patterns of CD4+ T cells triggered by different combinations of cytokines, metabolic regulation by IL2 in these cells, and their response to influenza infection. In doing so, we added multi-scale insights to single-scale studies and demonstrated its predictive power by discovering switch-like and oscillatory behaviors of CD4+ T cells that arise from nonlinear dynamics interwoven across three scales. We identified the inflamed lymph node's ability to retain naive CD4+ T cells as a key mechanism in generating these emergent behaviors. We envision our model and the generic framework encompassing it to serve as a tool for understanding cellular and molecular immunological problems through the lens of systems immunology.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções/imunologia , Modelos Imunológicos , Imunidade Adaptativa , Algoritmos , Linfócitos T CD4-Positivos/metabolismo , Biologia Computacional , Simulação por Computador , Citocinas/imunologia , Humanos , Infecções/genética , Infecções/metabolismo , Influenza Humana/imunologia , Método de Monte Carlo , Dinâmica não Linear , Análise Espaço-Temporal , Análise de Sistemas , Biologia de Sistemas
8.
Front Immunol ; 12: 697435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248999

RESUMO

Beyond all doubts, the exploration of outer space is a strategically important and priority sector of the national economy, scientific and technological development of every and particular country, and of all human civilization in general. A number of stress factors, including a prolonged confinement in a limited hermetically sealed space, influence the human body in space on board the spaceship and during the orbital flight. All these factors predominantly negatively affect various functional systems of the organism, in particular, the astronaut's immunity. These ground-based experiments allow to elucidate the effect of confinement in a limited space on both the activation of the immunity and the changes of the immune status in dynamics. Also, due to simulation of one or another emergency situation, such an approach allows the estimation of the influence of an additional psychological stress on the immunity, particularly, in the context of the reserve capacity of the immune system. A sealed chamber seems a convenient site for working out the additional techniques for crew members selection, as well as the countermeasures for negative changes in the astronauts' immune status. In this review we attempted to collect information describing changes in human immunity during isolation experiments with different conditions including short- and long-term experiments in hermetically closed chambers with artificial environment and during Antarctic winter-over.


Assuntos
Astronautas/psicologia , Espaços Confinados , Sistema Imunitário/fisiologia , Voo Espacial/psicologia , Estresse Psicológico/imunologia , Imunidade Adaptativa , Adulto , Regiões Antárticas , Simulação por Computador , Sistemas Ecológicos Fechados , Feminino , Humanos , Imunidade Inata , Masculino , Microbiota/imunologia , Pessoa de Meia-Idade , Pesquisa Espacial , Simulação de Ambiente Espacial , Astronave , Estresse Fisiológico , Fatores de Tempo , Adulto Jovem
9.
J Immunol Methods ; 495: 113073, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029621

RESUMO

Dendritic cells (DCs) play an essential role in the initiation of adaptive immune responses, but they are rare in all organs. The traditional methods used to increase the yield and purity of DCs are the early removal of granulocyte culture medium and the isolation of high-purity DCs by magnetic-activated cell sorting (MACS). This study provides a more rapid and economical optimization method to obtain more high-purity DCs. (i) We harvested 18% more bone marrow (BM) cells by using forceps to crack the epiphysis instead of cutting it with scissors during BM cell extraction. (ii) When the cells in the culture medium that is discarded on day 3 in the traditional method were centrifuged and then added back to the petri dish, the DC yield on day 5 increased by 61%. (iii) On the third day, the addition of fresh medium and the retention of the original medium rather than discarding it increased the number of DCs harvested on the fifth day by 137%. (i-iii) The improved method cost an average of 74% less than the conventional method and yielded the same number and function of cells. (iv) The initial number of BM cells was increased by 15% in 4-week-old mice compared with 8-week-old mice. (v) The Percoll density centrifugation (PDS) method was used to purify DCs on day 6 after induction, and the purity of the DCs was greater than 90%, which showed no significant difference from the MACS method. However, the yield of the PDS method increased by 21%. In addition, the PDS method has a lower cost, with an average purification cost of 4 CNY ($0.58) compared with 648 CNY ($93.25) for MACS, reducing the cost by 99%. Therefore, high-purity and high-yield DCs can be rapidly obtained through a five-step improvement in the process of BM cell extraction, induction and purification.


Assuntos
Imunidade Adaptativa , Células da Medula Óssea/imunologia , Separação Celular/métodos , Células Dendríticas/imunologia , Animais , Biomarcadores/metabolismo , Células da Medula Óssea/metabolismo , Proliferação de Células , Separação Celular/economia , Células Cultivadas , Técnicas de Cocultura , Redução de Custos , Análise Custo-Benefício , Células Dendríticas/metabolismo , Ativação Linfocitária , Masculino , Camundongos Endogâmicos C57BL , Fagocitose , Fenótipo , Fatores de Tempo , Fluxo de Trabalho
10.
Sci Rep ; 11(1): 909, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441700

RESUMO

Cladosporium cladosporioides causes asthma and superficial and deep infections, mostly in immunodeficient individuals and animals. This study aimed to investigate whether C. cladosporioides spores can enter the lungs through pulmonary circulation and influence pulmonary immune response. We intravenously injected mice with C. cladosporioides spore suspension and conducted several assays on the lungs. Pulmonary hemorrhage symptoms and congestion were most severe on days 1, 2, and 3 post-inoculation (PI). Extensive inflammatory cell infiltration occurred throughout the period of infection. More spores and hyphae colonizing the lungs were detected on days 1, 2, and 3 PI, and fewer spores and hyphae were observed within 21 d of infection. Numerous macrophages, dendritic cells, and neutrophils were observed on day 5 PI, along with upregulation of CD54, an intercellular adhesion molecule. Th1 and Th2 cells increased after infection; specifically, Th2 cells increased considerably on day 5 PI. These results suggest that days 2 and 5 PI represent the inflammatory peak in the lungs and that the Th2 and Th1 signaling pathways are potentially involved in pulmonary immune responses. In conclusion, the further adaptive immune responses played important roles in establishing effective pulmonary immunity against C. cladosporioides systemic infections based on innate immune responses.


Assuntos
Imunidade Adaptativa/imunologia , Cladosporium/imunologia , Pneumopatias Fúngicas/imunologia , Animais , Asma/imunologia , Cladosporium/metabolismo , Cladosporium/patogenicidade , Modelos Animais de Doenças , Feminino , Imunidade Inata/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Pneumonia/imunologia , Esporos Fúngicos/imunologia , Esporos Fúngicos/patogenicidade , Células Th2/imunologia
12.
Front Immunol ; 12: 797919, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34975908

RESUMO

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.


Assuntos
Imunidade Adaptativa/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Convalescença , SARS-CoV-2/imunologia , Adolescente , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , COVID-19/virologia , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Humoral/imunologia , Imunoglobulina G/imunologia , Masculino , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
13.
Nat Rev Rheumatol ; 17(2): 81-97, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33318665

RESUMO

Biologic agents have become a core component of therapeutic strategies for many inflammatory rheumatic diseases. However, perhaps reflecting the specificity and generally high affinity of biologic agents, these therapeutics have been used by rheumatologists with less consideration of their pharmacokinetics than that of conventional synthetic DMARDs. Immunogenicity was recognized as a potential limitation to the use of biologic agents at an early stage in their development, although regulatory guidance was relatively limited and assays to measure immunogenicity were less sophisticated than today. The advent of biosimilars has sparked a renewed interest in immunogenicity that has resulted in the development of increasingly sensitive assays, an enhanced appreciation of the pharmacokinetic consequences of immunogenicity and the development of comprehensive and specific guidance from regulatory authorities. As a result, rheumatologists have a greatly improved understanding of the field in general, including the factors responsible for immunogenicity, its potential clinical consequences and the implications for everyday treatment. In some specialties, immunogenicity testing is becoming a part of routine clinical management, but definitive evidence of its cost-effectiveness in rheumatology is awaited.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Fatores Biológicos/farmacocinética , Doenças Reumáticas/tratamento farmacológico , Reumatologia/normas , Imunidade Adaptativa/imunologia , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Fatores Biológicos/imunologia , Fatores Biológicos/uso terapêutico , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/uso terapêutico , Análise Custo-Benefício , Humanos , Doenças Reumáticas/imunologia , Reumatologistas/estatística & dados numéricos , Reumatologia/economia
14.
Front Public Health ; 8: 566114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224915

RESUMO

Throughout history, the human race has often faced pandemics with substantial numbers of fatalities. As the COVID-19 pandemic has now affected the whole planet, even countries with moderate to strong healthcare support and expenditure have struggled to contain disease transmission and casualties. Countries affected by COVID-19 have different demographics, socioeconomic, and lifestyle health indicators. In this context, it is important to find out to what extent these parametric variations are modulating disease outcomes. To answer this, this study selected demographic, socioeconomic, and health indicators e.g., population density, percentage of the urban population, median age, health expenditure per capita, obesity, diabetes prevalence, alcohol intake, tobacco use, case fatality of non-communicable diseases (NCDs) as independent variables. Countries were grouped according to these variables and influence on dependent variables e.g., COVID-19 positive tests, case fatality, and case recovery rates were statistically analyzed. The results suggested that countries with variable median age had a significantly different outcome on positive test rate (P < 0.01). Both the median age (P = 0.0397) and health expenditure per capita (P = 0.0041) showed a positive relation with case recovery. An increasing number of tests per 100 K of the population showed a positive and negative relationship with the number of positives per 100 K population (P = 0.0001) and the percentage of positive tests (P < 0.0001), respectively. Alcohol intake per capita in liter (P = 0.0046), diabetes prevalence (P = 0.0389), and NCDs mortalities (P = 0.0477) also showed a statistical relation to the case fatality rate. Further analysis revealed that countries with high healthcare expenditure along with high median age and increased urban population showed more case fatality but also had a better recovery rate. Investment in the health sector alone is insufficient in controlling the severity of the pandemic. Intelligent and sustainable healthcare both in urban and rural settings and healthy lifestyle acquired immunity may reduce disease transmission and comorbidity induced fatalities, respectively.


Assuntos
COVID-19 , Pandemias , Imunidade Adaptativa , Atenção à Saúde , Gastos em Saúde , Humanos , Estilo de Vida , Pandemias/prevenção & controle , SARS-CoV-2
15.
mSphere ; 5(6)2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177214

RESUMO

Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We monitored shedding of viral RNA and infectious virus and characterized the immune response kinetics of the first five patients quarantined in Geneva, Switzerland. High viral loads and infectious virus shedding were observed from the respiratory tract despite mild symptoms, with isolation of infectious virus and prolonged positivity by reverse transcriptase PCR (RT-PCR) until days 7 and 19 after symptom onset, respectively. Robust innate responses characterized by increases in activated CD14+ CD16+ monocytes and cytokine responses were observed as early as 2 days after symptom onset. Cellular and humoral severe acute respiratory syndrome (SARS)-CoV-2-specific adaptive responses were detectable in all patients. Infectious virus shedding was limited to the first week after symptom onset. A strong innate response, characterized by mobilization of activated monocytes during the first days of infection and SARS-CoV-2-specific antibodies, was detectable even in patients with mild disease.IMPORTANCE This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms.


Assuntos
Imunidade Adaptativa , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Imunidade Inata , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Carga Viral , Eliminação de Partículas Virais , Adulto , Idoso , Anticorpos Antivirais/metabolismo , Betacoronavirus/isolamento & purificação , Biomarcadores/metabolismo , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Citocinas/metabolismo , Humanos , Cinética , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , SARS-CoV-2 , Índice de Gravidade de Doença
16.
Genes (Basel) ; 11(11)2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33105610

RESUMO

We report the development of a multigene gene expression assay on the BioMark HD platform for the evaluation of immune competence (ImCom) in farmed Atlantic salmon. The first version of the assay included 92 genes selected on the basis of transcriptome analyses in 54 trials that challenged the immune system; annotations were taken into account to represent the key pathways of innate and adaptive immunity. ImCom was tested on samples collected from seven independent projects. Fish were reared from the start feeding to eight months in the sea at eight units in different parts of Norway. Several tissues were analyzed. Linear discriminant analysis (LDA) showed that no more than 10 genes were required to separate groups, and a set of 46 immune genes was sufficient for any task. The second version of the assay was tested in the gills of two groups of high-performing healthy smolts and in groups with intermediate and high mortality rates (IM and HM, respectively). A set of 645 gill samples from clinically healthy Atlantic salmon was used as a reference. The IM group showed general suppression of immunity. All HM group salmon were above the threshold by the squared deviation from the reference. This group showed marked upregulation of genes involved in acute stress and inflammation: mmp-9, mmp-13, hsp70, il-1b, lect2, and cathelicidin. Further work will clarify the boundaries of the norm and explore various cases of impaired immunity.


Assuntos
Imunidade Adaptativa/genética , Perfilação da Expressão Gênica/métodos , Imunidade Inata/genética , Salmo salar/genética , Salmo salar/imunologia , Imunidade Adaptativa/imunologia , Animais , Brânquias/imunologia , Imunidade Inata/imunologia , Herança Multifatorial/genética , Reação em Cadeia da Polimerase/métodos , Transcriptoma/genética
17.
Sci Transl Med ; 12(546)2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493791

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Imunidade Adaptativa , Antígenos Virais/análise , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Técnicas de Laboratório Clínico/economia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Custos e Análise de Custo , Reações Cruzadas , Humanos , Imunidade Inata , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , RNA Viral/análise , RNA Viral/genética , SARS-CoV-2 , Testes Sorológicos/métodos , Pesquisa Translacional Biomédica , Estados Unidos/epidemiologia , Carga Viral/imunologia
18.
J Immunol ; 205(1): 12-19, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32423917

RESUMO

The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for the infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from the infection, those individuals presenting with critical symptoms are in urgent need of effective treatment options. Emerging data related to mechanism of severity and potential therapies for patients presenting with severe symptoms are scattered and therefore require a comprehensive analysis to focus research on developing effective therapeutics. A critical literature review suggests that the severity of SARS-CoV-2 infection is associated with dysregulation of inflammatory immune responses, which in turn inhibits the development of protective immunity to the infection. Therefore, the use of therapeutics that modulate inflammation without compromising the adaptive immune response could be the most effective therapeutic strategy.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Imunidade Adaptativa , Fatores Etários , Animais , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/patologia , Disparidades nos Níveis de Saúde , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Fatores Sexuais , Viremia/imunologia , Viremia/patologia
19.
Rev Med Virol ; 30(4): e2113, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32420674

RESUMO

The pandemic of 2019 novel coronavirus (SARS-CoV-2019), reminiscent of the 2002-SARS-CoV outbreak, has completely isolated countries, disrupted health systems and partially paralyzed international trade and travel. In order to be better equipped to anticipate transmission of this virus to new regions, it is imperative to track the progress of the virus over time. This review analyses information on progression of the pandemic in the past 3 months and systematically discusses the characteristics of SARS-CoV-2019 virus including its epidemiologic, pathophysiologic, and clinical manifestations. Furthermore, the review also encompasses some recently proposed conceptual models that estimate the spread of this disease based on the basic reproductive number for better prevention and control procedures. Finally, we shed light on how the virus has endangered the global economy, impacting it both from the supply and demand side.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Imunidade Adaptativa , Antivirais/uso terapêutico , Número Básico de Reprodução , Betacoronavirus/classificação , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Comércio , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Economia , Genoma Viral , Humanos , Modelos Teóricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , SARS-CoV-2 , Replicação Viral , Tratamento Farmacológico da COVID-19
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA