32 results on '"Alcaraz-Serna A"'
Search Results
2. Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients
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Fallet, Benedict, Foglierini, Mathilde, Porret, Raphael, Alcaraz-Serna, Ana, Sauvage, Christophe, Jenelten, Raphael, Caplanusi, Teofila, Gilliet, Michel, Perez, Laurent, Fenwick, Craig, Genolet, Raphael, Harari, Alexandre, Bobisse, Sara, Gottardo, Raphael, Pantaleo, Giuseppe, and Muller, Yannick D.
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- 2023
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3. Thérapie cellulaire CAR-T dans le traitement des maladies auto-immunes
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Alcaraz-Serna, Ana, primary, Porret, Raphaël, additional, Trueb, Lionel, additional, Ribi, Camillo, additional, Seebach, Jörg, additional, and Muller, Yannick D., additional
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- 2024
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4. COVID-19 severity associates with pulmonary redistribution of [CD1c.sup.+] DCs and inflammatory transitional and nonclassical monocytes
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Sanchez-Cerrillo, Ildefonso, Landete, Pedro, Aldave, Beatriz, Sanchez-Alonso, Santiago, Sanchez-Azofra, Ana, Marcos-Jimenez, Ana, Avalos, Elena, Alcaraz-Serna, Ana, de los Santos, Ignacio, Mateu-Albero, Tamara, Esparcia, Laura, Lopez-Sanz, Celia, Martinez-Fleta, Pedro, Gabrie, Ligia, del Campo Guerola, Luciana, de la Fuente, Hortensia, Calzada, Maria J., Gonzalez-Alvaro, Isidoro, Alfranca, Arantzazu, Sanchez-Madrid, Francisco, Munoz-Calleja, Cecilia, Soriano, Joan B., Ancochea, Julio, and Martin-Gayo, Enrique
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Epidemics -- Control -- Spain ,Dendritic cells -- Health aspects ,Immune response -- Observations ,COVID-19 -- Complications and side effects -- Care and treatment ,Health care industry - Abstract
SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of [CD8.sup.+] T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector [CD8.sup.+] T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and [CD1c.sup.+] conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection., Introduction The new SARS-CoV-2 virus causing coronavirus disease 2019 (COVID-19) has unleashed the current pandemic. Individuals infected with this pathogen can either remain asymptomatic or progress from mild to severe [...]
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- 2020
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5. Basophil activation tests with cryopreserved mRNA-based COVID-19 vaccines
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Alcaraz-Serna, Ana, primary, Noto, Alessandra, additional, Ermellino, Laura, additional, Monzambani-Banderet, Véronique, additional, Tommasini, Francesco, additional, Stehlin, Florian, additional, Girard, Cedric, additional, Perreau, Matthieu, additional, and Muller, Yannick D., additional
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- 2023
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6. Extracellular Vesicle-Mediated Immune Regulation of Tissue Remodeling and Angiogenesis After Myocardial Infarction
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Santiago Sánchez-Alonso, Ana Alcaraz-Serna, Francisco Sánchez-Madrid, and Arantzazu Alfranca
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small EVs ,tissue remodeling ,myocardial infarction ,immune system ,angiogenesis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Myocardial ischemia-related disorders constitute a major health problem, being a leading cause of death in the world. Upon ischemia, tissue remodeling processes come into play, comprising a series of inter-dependent stages, including inflammation, cell proliferation and repair. Neovessel formation during late phases of remodeling provides oxygen supply, together with cellular and soluble components necessary for an efficient myocardial reconstruction. Immune system plays a central role in processes aimed at repairing ischemic myocardium, mainly in inflammatory and angiogenesis phases. In addition to cellular components and soluble mediators as chemokines and cytokines, the immune system acts in a paracrine fashion through small extracellular vesicles (EVs) release. These vesicular structures participate in multiple biological processes, and transmit information through bioactive cargoes from one cell to another. Cell therapy has been employed in an attempt to improve the outcome of these patients, through the promotion of tissue regeneration and angiogenesis. However, clinical trials have shown variable results, which put into question the actual applicability of cell-based therapies. Paracrine factors secreted by engrafted cells partially mediate tissue repair, and this knowledge has led to the hypothesis that small EVs may become a useful tool for cell-free myocardial infarction therapy. Current small EVs engineering strategies allow delivery of specific content to selected cell types, thus revealing the singular properties of these vesicles for myocardial ischemia treatment.
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- 2018
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7. Aurora A controls CD8+ T cell cytotoxic activity and antiviral response
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Bustos-Morán, Eugenio, Blas-Rus, Noelia, Alcaraz-Serna, Ana, Iborra, Salvador, González-Martínez, José, Malumbres, Marcos, and Sánchez-Madrid, Francisco
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- 2019
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8. Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets
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Carlos Cuesta-Mateos, Ana Alcaraz-Serna, Beatriz Somovilla-Crespo, and Cecilia Muñoz-Calleja
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monoclonal antibody ,immunotherapy ,hematological malignancies ,non-lineage antigens ,mechanism of action ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Today, monoclonal antibodies (mAbs) are a widespread and necessary tool for biomedical science. In the hematological cancer field, since rituximab became the first mAb approved by the Food and Drug Administration for the treatment of B-cell malignancies, a number of effective mAbs targeting lineage-specific antigens (LSAs) have been successfully developed. Non-LSAs (NLSAs) are molecules that are not restricted to specific leukocyte subsets or tissues but play relevant pathogenic roles in blood cancers including the development, proliferation, survival, and refractoriness to therapy of tumor cells. In consequence, efforts to target NLSAs have resulted in a plethora of mAbs—marketed or in development—to achieve different goals like neutralizing oncogenic pathways, blocking tumor-related chemotactic pathways, mobilizing malignant cells from tumor microenvironment to peripheral blood, modulating immune-checkpoints, or delivering cytotoxic drugs into tumor cells. Here, we extensively review several novel mAbs directed against NLSAs undergoing clinical evaluation for treating hematological malignancies. The review focuses on the structure of these antibodies, proposed mechanisms of action, efficacy and safety profile in clinical studies, and their potential applications in the treatment of hematological malignancies.
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- 2018
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9. Procalcitonin concentration in the emergency department predicts 30-day mortality in COVID-19 better than the lymphocyte count, the neutrophil-tolymphocyte ratio, or the C-reactive protein level
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Pedro, López-Ayala, Ana, Alcaraz-Serna, Adrián, Valls Carbó, Mª Ángeles, Cuadrado Cenzual, María José, Torrejón Martínez, Amanda, López Picado, Carmen, Martínez Valero, Juande D, Miranda, Cristina, Díaz Del Arco, Gabriel, Cozar López, María Del Mar, Suárez-Cadenas, Pablo, Jerez Fernández, Beatriz, Angós, Esther, Rodríguez Adrada, Eduardo, Cardassay, Enrique, Del Toro, David, Chaparro, María Teresa, Montalvo Moraleda, Carolina, Espejo Paeres, Miguel Ángel, García Briñón, Víctor, Hernández Martín-Romo, Luis, Ortega, Cristina, Fernández Pérez, Mercedes, Martínez-Novillo, Juan Jorge, González Armengol, Juan, González Del Castillo, Christian E, Mueller, and F Javier, Martín-Sánchez
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Calcitonin ,Male ,C-Reactive Protein ,Neutrophils ,COVID-19 ,Humans ,Lymphocyte Count ,Middle Aged ,Emergency Service, Hospital ,Procalcitonin ,Aged ,Retrospective Studies - Abstract
Although many demographic and clinical predictors of mortality have been studied in relation to COVID-19, little has been reported about the prognostic utility of inflammatory biomarkers.Retrospective cohort study. All patients with laboratory-confirmed COVID-19 treated in a hospital emergency department were included consecutively if baseline measurements of the following biomarkers were on record: lymphocyte counts, neutrophil-to-lymphocyte ratio NRL, and C-reactive protein (CRP) and procalcitonin (PCT) levels. We analyzed associations between the biomarkers and all-cause 30-day mortality using Cox regression models and dose-response curves.We included 896 patients, 151 (17%) of whom died within 30 days. The median (interquartile range) age was 63 (51-78) years, and 494 (55%) were men. NLR, CRP and PCT levels at ED presentation were higher, while lymphocyte counts were lower, in patients who died compared to those who survived (P .001). The areas under the receiver operating characteristic curves revealed the PCT concentration (0.79; 95% CI, 0.75-0.83) to be a better predictor of 30-day mortality than the lymphocyte count (0.70; 95% CI, 0.65-0.74; P .001), the NLR (0.74; 95% CI, 0.69-0.78; P = .03), or the CRP level (0.72; 95% CI, 0.68-0.76; P .001). The proposed PCT concentration decision points for use in emergency department case management were 0.06 ng/L (negative) and 0.72 ng/L (positive). These cutoffs helped classify risk in 357 patients (40%). Multivariable analysis demonstrated that the PCT concentration had the strongest association with mortality.PCT concentration in the emergency department predicts all-cause 30-day mortality in patients with COVID-19 better than other inflammatory biomarkers.Existen múltiples variables demográficas y clínicas predictivas de mortalidad en pacientes con COVID-19. Sin embargo, hay menos información sobre el valor pronóstico de los biomarcadores inflamatorios.Estudio de cohorte retrospectivo. Se incluyeron de forma consecutiva todos los pacientes con COVID-19, confirmado por laboratorio, atendidos en un servicio de urgencias hospitalario (SUH) y con valor basal de los siguientes biomarcadores: recuento linfocitario, índice neutrófilo/linfocito (INL), proteína C reactiva (PCR) y procalcitonina (PCT). La relación entre los biomarcadores y la mortalidad total a 30 días se analizó mediante una regresión de Cox y gráficos de dosis-respuesta.Se incluyeron 896 pacientes, 151 (17%) fallecieron en los primeros 30 días. La mediana de edad fue de 63 años (51-78) y 494 (55%) eran hombres. El valor de INL, PCR y PCT fue mayor, mientras que el recuento linfocitario fue menor, en los pacientes que fallecieron respecto a los que sobrevivieron (p 0,001). La PCT fue superior al recuento linfocitario, INL y PCR en la predicción de mortalidad a 30 días (ABC 0,79 [IC 95%: 0,75-0,83] vs 0,70 [IC 95%: 0,65-0,74], p 0,001; 0,74 [IC 95%: 0,69-0,78], p = 0,03; y 0,72 [IC 95%: 0,68-0,76], p 0,001). Los puntos de decisión de PCT propuestos, 0,06 ng/l para exclusión y 0,72 ng/l para inclusión de muerte a 30 días, podrían facilitar la toma de decisiones en urgencias. Hubo 357 pacientes (40%) con valores de PCT en estas categorías. El análisis multivariable mostró una mayor asociación con la mortalidad para PCT que en los otros biomarcadores estudiados.PCT es el biomarcador con mejor capacidad para predecir mortalidad a 30 días por cualquier causa en pacientes con COVID-19 valorados en un SUH.
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- 2022
10. COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes
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Hortensia de la Fuente, Pedro Martínez-Fleta, Ignacio Santos, Ana Alcaraz-Serna, Elena Ávalos, Ana Marcos-Jimenez, Arantzazu Alfranca, Beatriz Aldave, Ana Sanchez-Azofra, Ildefonso Sánchez-Cerrillo, Isidoro González-Álvaro, Luciana del Campo Guerola, Tamara Mateu-Albero, Pedro Landete, Maria J. Calzada, Santiago Sánchez-Alonso, Francisco Sánchez-Madrid, Enrique Martín-Gayo, Ligia Gabrie, Laura Esparcia, Joan B. Soriano, Celia López-Sanz, Cecilia Muñoz-Calleja, and Julio Ancochea
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0301 basic medicine ,ARDS ,Lung ,Myeloid ,business.industry ,T cell ,Inflammation ,General Medicine ,medicine.disease ,Pathogenesis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,030220 oncology & carcinogenesis ,Immunology ,medicine ,medicine.symptom ,business ,CD8 - Abstract
SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.
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- 2020
11. Procalcitonin concentration in the emergency department predicts 30-day mortality in COVID-19 better than the lymphocyte count, the neutrophil-tolymphocyte ratio, or the C-reactive protein level
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López-Ayala, Pedro, Alcaraz-Serna, Ana, Valls Carbó, Adrián, Cuadrado Cenzual, Mª Ángeles, Torrejón Martínez, María José, López Picado, Amanda, Martínez Valero, Carmen, Miranda, Juande D., Díaz Del Arco, Cristina, Cozar López, Gabriel, Suárez-Cadenas, María Del Mar, Jerez Fernández, Pablo, Angós, Beatriz, Rodríguez Adrada, Esther, Cardassay, Eduardo, Del Toro, Enrique, Chaparro, David, Montalvo Moraleda, María Teresa, Espejo Paeres, Carolina, García Briñón, Miguel Ángel, Hernández Martín-Romo, Víctor, Ortega, Luis, Fernández Pérez, Cristina, Martínez-Novillo, Mercedes, González Armengol, Juan Jorge, González Del Castillo, Juan, Mueller, Christian E., Martín-Sánchez, F. Javier, and IdIssc-Covid-Taskforce
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- 2022
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12. Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells
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Ana Alcaraz-Serna, Centro Nacional de Investigaciones Cardiovasculares (Cnic), Madrid, Spain., Enrique Vázquez, Ester Marina-Zárate, Juliana Barreto de Alburquerque, Jens V. Stein, Erika Lorenzo-Vivas, Fátima Sánchez-Cabo, Manuel Gómez, Spain. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (Cibercv), Francisco Sánchez-Madrid, Diego Calzada-Fraile, Irene Fernández-Delgado, Ana Dopazo, Nora Ruef, Daniel Torralba, Eugenio Bustos-Morán, and Almudena R. Ramiro
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Transcriptome ,Biology ,Reprogramming ,Immunological synapse ,Cell biology ,Epigenomics - Published
- 2021
13. Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells
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Fátima Sánchez-Cabo, Ana Dopazo, Francisco Sánchez-Madrid, Eugenio Bustos-Morán, Jens V. Stein, Daniel Torralba, Manuel Gómez, Ana Alcaraz-Serna, Juliana Barreto de Alburquerque, Nora Ruef, Erika Lorenzo-Vivas, Enrique Vázquez, Diego Calzada-Fraile, Irene Fernández-Delgado, Ester Marina-Zárate, Almudena R. Ramiro, UAM. Departamento de Medicina, Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Fundación Ramón Areces, Fundación BBVA, Fundación La Caixa, Centro de Investigación Biomedica en Red - CIBER, European Regional Development Fund (ERDF/FEDER), Ministerio de Ciencia, Innovación y Universidades (España), and Fundación ProCNIC
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Receptors, CCR7 ,Medicina ,T cell ,Immunology ,Population ,Antigen presentation ,T cells ,chemical and pharmacologic phenomena ,Biology ,migratory capacity ,Immunological synapse ,03 medical and health sciences ,transcriptomics ,0302 clinical medicine ,Cell Movement ,Postsynaptic potential ,medicine ,dendritic cells ,education ,Research Articles ,030304 developmental biology ,Epigenomics ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,CCL19 ,SciAdv r-articles ,Life Sciences ,hemic and immune systems ,biochemical phenomena, metabolism, and nutrition ,Cell biology ,medicine.anatomical_structure ,Synapses ,epigenomics ,Lymph Nodes ,Transcriptome ,Reprogramming ,Research Article ,030215 immunology - Abstract
Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, we describe that postsynaptic DCs switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor Ccr7 as a proof-of-concept gene that is increased in postsynaptic DCs. Consistent with our epigenomic observations, postsynaptic DCs migrate more efficiently toward CCL19 in vitro and display enhanced homing to draining lymph nodes in vivo. This work describes a previously unknown DC population whose transcriptomics, epigenomics, and migratory capacity change in response to their cognate contact with T cells, This study was supported by grant SAF2017-82886-R from the Spanish Ministry of Economy and Competitiveness (MINECO), grant S2017/BMD-3671-INFLAMUNE-CM from the Comunidad de Madrid, a grant from the Ramón Areces Foundation “Ciencias de la Vida y la Salud” (XIX Concurso-2018), a grant from Ayudas Fundación BBVA a Equipos de Investigación Científica (BIOMEDICINA-2018), the Fundació Marató TV3 (grant 122/C/2015), “la Caixa” Banking Foundation (HR17-00016), BIOIMID (PIE13/041) from Instituto de Salud Carlos III, CIBER Cardiovascular (CB16/11/00272), and Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). D.C.-F. is supported by a Fellowship from “la Caixa” Foundation (LCF/BQ/DR19/11740010). I.F.-D. is supported by a Fellowship from the Spanish Ministry of Science, Innovation, and Universities (FPU15/02539). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505)
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- 2021
14. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID‐19 patients
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Hugh T. Reyburn, Luciana del Campo Guerola, Santiago Sánchez-Alonso, Hortensia de la Fuente, Arantzazu Alfranca, Ligia Gabrie, Maria J. Calzada, José Miguel Rodríguez-Frade, Ana Marcos-Jimenez, Pedro Martínez-Fleta, Mar Valés-Gómez, Miguel Sampedro-Núñez, Enrique Martin-Gayo, Cecilia Muñoz-Calleja, Ildefonso Sánchez-Cerrillo, Tamara Mateu-Albero, Ana Alcaraz-Serna, José M. Casasnovas, Francisco Sánchez-Madrid, Margarita López-Trascasa, Celia López-Sanz, Santos Castañeda, Laura Esparcia, Isidoro González-Álvaro, UAM. Departamento de Medicina, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación 'la Caixa', European Commission, and Comunidad de Madrid
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0301 basic medicine ,Male ,Coronavirus disease 2019 (COVID-19) ,Medicina ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Immunity to infection ,immunoglobulins ,macromolecular substances ,SARS‐CoV‐2 ,03 medical and health sciences ,Clinical ,0302 clinical medicine ,Immune system ,Immunity ,COVID‐19 ,Lymphopenia ,Follicular phase ,Immunology and Allergy ,Humans ,complement ,Lymphocyte Count ,Aged ,B-Lymphocytes ,Respiratory Distress Syndrome ,biology ,Research Article|Clinical ,SARS-CoV-2 ,COVID-19 ,Complement C5 ,Complement C4 ,Complement C3 ,T-Lymphocytes, Helper-Inducer ,Middle Aged ,immunity ,Peripheral blood ,Immunoglobulin A ,Killer Cells, Natural ,030104 developmental biology ,Immunoglobulin M ,Immunoglobulin G ,Humoral immunity ,biology.protein ,Female ,Antibody ,030215 immunology ,Research Article - Abstract
SARS‐CoV‐2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID‐19. We investigated whether the specific immune responses in the peripheral blood of 276 patients associated to severity and progression of COVID‐19. At admission, dramatic lymphopenia of T, B and NK cells associated to severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56‐CD16+ NK‐cells increased. Regarding humoral immunity, levels of IgM, IgA and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID‐19 patients, associating severity with an imbalanced humoral response and identifying new targets for therapeutic intervention., The study was funded by grants SAF2017-82886-R to FS-M from the Ministerio de Economía y Competitividad, and from “La Caixa Banking Foundation” (HR17-00016) to FS-M. Grant PI018/01163 to CMC and grant PI19/00549 to AA were funded by Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain. SAF2017-82886-R, PI018/01163 and PI19/00549 grants were also cofunded by European Regional Development Fund, ERDF/FEDER. This work has been funded by grants Fondo Supera COVID (CRUE-Banco de Santander) to FSM, and “Ayuda Covid 2019” from Comunidad de Madrid.
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- 2020
15. Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells
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Alcaraz-Serna, Ana, primary, Bustos-Morán, Eugenio, additional, Fernández-Delgado, Irene, additional, Calzada-Fraile, Diego, additional, Torralba, Daniel, additional, Marina-Zárate, Ester, additional, Lorenzo-Vivas, Erika, additional, Vázquez, Enrique, additional, de Alburquerque, Juliana Barreto, additional, Ruef, Nora, additional, Gómez, Manuel José, additional, Sánchez-Cabo, Fátima, additional, Dopazo, Ana, additional, Stein, Jens V., additional, Ramiro, Almudena, additional, and Sánchez-Madrid, Francisco, additional
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- 2021
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16. Author response for 'Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID‐19 patients'
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Luciana del Campo Guerola, Maria J. Calzada, Santos Castañeda, José M. Casasnovas, Santiago Sánchez-Alonso, Ana Marcos-Jimenez, Celia López-Sanz, Ana Alcaraz-Serna, Miguel Sampedro-Núñez, Hugh T. Reyburn, Francisco Sánchez-Madrid, Margarita López-Trascasa, Cecilia Muñoz-Calleja, Ligia Gabrie, Arantzazu Alfranca, Ildefonso Sánchez-Cerrillo, Isidoro González-Álvaro, José Miguel Rodríguez-Frade, Tamara Mateu-Albero, Enrique Martin-Gayo, Mar Valés-Gómez, Hortensia de la Fuente, Laura Esparcia, and Pedro Martínez-Fleta
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Consumption (economics) ,Coronavirus disease 2019 (COVID-19) ,Immunology ,biology.protein ,Biology ,Antibody ,Complement (complexity) - Published
- 2020
17. IL-6 serum levels predict severity and response to Tocilizumab in COVID-19: an observational study
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José María Galván-Román, Sebastián C. Rodríguez-García, Emilia Roy-Vallejo, Ana Marcos-Jiménez, Santiago Sánchez-Alonso, Carlos Fernández-Díaz, Ana Alcaraz-Serna, Tamara Mateu-Albero, Pablo Rodríguez-Cortes, Ildefonso Sánchez-Cerrillo, Laura Esparcia, Pedro Martínez-Fleta, Celia López-Sanz, Ligia Gabrie, Luciana del Campo Guerola, Carmen Suárez-Fernández, Julio Ancochea, Alfonso Canabal, Patricia Albert, Diego A. Rodríguez-Serrano, Juan Mariano Aguilar, Carmen del Arco, Ignacio de los Santos, Lucio García-Fraile, Rafael de la Cámara, José María Serra, Esther Ramírez, Tamara Alonso, Pedro Landete, Joan B. Soriano, Enrique Martín-Gayo, Arturo Fraile Torres, Nelly Daniela Zurita Cruz, Rosario García-Vicuña, Laura Cardeñoso, Francisco Sánchez-Madrid, Arantzazu Alfranca, Cecilia Muñoz-Calleja, Isidoro González-Álvaro, Teresa Alvarado, Pablo Martínez, Francisco Javier de la Cuerda Llorente, Natalia Villalba, Mónica Negro, Elvira Contreras, Ana del Rey, Cristina Santiago, Manuel Junquera, Raquel Caminero, Francisco Javier Val, Sonia González, Marta Caño, Isabel López, Andrés von Wernitz, Bárbara Retana, Iñigo Guerra, Jorge Sorando, Lydia Chao, María José Cárdenas, Verónica Espiga, Pablo Chicharro, Pedro Rodríguez, Iñigo Hernando Alday, Miguel Sampedro, Jorge Prada, Eukene Rojo Aldama, Yolanda Real, María Caldas, Sergio Casabona, Aitor Lanas-Gimeno, Rafael de la Camara, Angela Figuera Alvárez, Beatriz Aguadol, Alberto Morell, Amparo Ibáñez Zurriaga, María Pérez Abanades, Silvia Ruiz García, Tomás Gallego Aranda, María Ruiz, Concepción Martínez Nieto, Javier Aspa, Elena Fernández, Ma José Calzada, Reyes Tejedor, Judit Iglesias, Fernando Suarez, Juan Antonio Sánchez, Beatriz Abad, Carmen Suarez, Emilia Roy, Jesus Sanz, Eduardo Sanchez, Fernando Moldenhauer, Pedro Casado, Jose Curbelo, Angela Gutierrez, Azucena Bautista, Nuria Ruiz Giménez, Angelica Fernandez, Pedro Parra, Berta Moyano, Ana Barrios, Diego Real de Asua, Beatriz Sanchez, Carmen Saez, Marianela Ciudad, Desiré Navas, Laura Cardeñoso Domingo, María del Carmen Cuevas Torresano, Diego Domingo García, Teresa Alarcón Cavero, Alicia García Blanco, Alexandra Martín Ramírez, María Auxiliadora Semiglia Chong, Ainhoa Gutiérrez Cobos, Arturo Manuel Fraile Torres, Carmen Sanchez-Gonzalez, Antonio Fernádez Perpén, Carolina Díaz Pérez, Joan Soriano, Carolina Cisneros, Elena García Castillo, Francisco Javier García Pérez, Rosa María Girón, Celeste Marcos, Enrique Zamora, Patricia García García, Santos Castañeda, Sebastián Rodríguez-García, Irene Llorente Cubas, Eva G. Tomero, Noelia García Castañeda, Ana Ma Ortiz, Cristina Valero, Miren Uriarte, and Nuria Montes
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0301 basic medicine ,ARDS ,CAR, chimeric antigen receptor ,medicine.medical_treatment ,Invasive Mechanical Ventilation ,chemistry.chemical_compound ,0302 clinical medicine ,SatO2, mean oxygen saturation ,Interquartile range ,Fraction of inspired oxygen ,Immunology and Allergy ,030212 general & internal medicine ,COVID-19, coronavirus disease 2019 ,PaO2/FiO2, arterial oxygen tension/fraction of inspired oxygen ratio ,TNF, tumor necrosis factor ,AUC, Area under curve ,AEMPS, Spanish Agency for Drugs and Health Devices ,Tocilizumab ,CRS, cytokine release syndrome ,PCT, procalcitonin ,Cytokine release syndrome ,CRP, C-reactive protein ,LR, negative likelihood ratio ,medicine.medical_specialty ,Immunology ,LR+, positive likelihood ratio ,Article ,03 medical and health sciences ,Internal medicine ,medicine ,TCZ, Tocilizumab ,Survival rate ,ARDS, acute respiratory distress syndrome ,IQR, interquartile range ,Mechanical ventilation ,business.industry ,Interleukin-6 ,COVID-19 ,Odds ratio ,PaO2, arterial oxygen tension ,medicine.disease ,IL, interleukin ,ROC, receiver operating characteristic ,030104 developmental biology ,IMV, invasive mechanical ventilation ,chemistry ,COPD, chronic obstructive pulmonary disease ,STROBE, Strengthening the Reporting of Observational Studies in Epidemiology ,business ,SD, standard deviation - Abstract
Background COVID-19 patients can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation (IMV). Since interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective To determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods Retrospective observational study performed in hospitalized patients diagnosed of COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with pre- and post-administration of TCZ. Multivariable logistic and linear regressions, and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio (PaO2/FiO2) or mortality. Results One hundred and forty-six patients were studied, predominantly male (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels>30 pg/ml was the best predictor for IMV (OR:7.1; p30 pg/ml predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration., Baseline IL-6 serum levels>30 pg/ml identify severe COVID-19 patients and should be used to guide the intervention with IL-6R inhibitors, aiming to improve their use in an uncertain and evolving therapeutic scenario.
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- 2020
18. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19
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Laura Esparcia, Miguel Sampedro-Núñez, Enrique Martin-Gayo, Arantzazu Alfranca, Ildefonso Sánchez-Cerrillo, Luciana del Campo Guerola, Santos Castañeda, Ana Marcos-Jimenez, Ligia Gabrie, Pedro Martínez-Fleta, Ana Alcaraz-Serna, Santiago Sánchez-Alonso, Tamara Mateu-Albero, Celia López-Sanz, Margarita López-Trascasa, Francisco Sánchez-Madrid, Hortensia de la Fuente, Isidoro González-Álvaro, Maria J. Calzada, and Cecilia Muñoz-Calleja
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Antibody-dependent cell-mediated cytotoxicity ,medicine.diagnostic_test ,biology ,business.industry ,Flow cytometry ,Complement system ,Pathogenesis ,Immune system ,Peripheral blood lymphocyte ,Immunology ,Humoral immunity ,medicine ,biology.protein ,Antibody ,business - Abstract
BackgroundSARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the pathogenesis and outcome of COVID-19. We aimed to investigate which specific responses from either cellular or humoral immunity associate to severity and progression of COVID-19.MethodsA cohort of 276 patients classified in mild, moderate and severe, was studied. Peripheral blood lymphocyte subpopulations were quantified by flow cytometry, and immunoglobulins and complement proteins by nephelometry.ResultsAt admission, dramatic lymphopenia of T, B and NK cells associated to severity. However, only the proportion of B cells increased, while T and NK cells appeared unaffected. Accordingly, the number of plasma cells and circulating follicular helper T cells (cTfh) increased, but levels of IgM, IgA and IgG were unaffected. When degrees of severity were considered, IgG was lower in severe patients, suggesting an IgG consumption by complement activation or antibody-dependent cellular cytotoxicity (ADCC). Activated CD56-CD16+ NK-cells, which mediate ADCC, were increased. Regarding complement, C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, compared to healthy donors. Moreover, IgG and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier.ConclusionOur study provides important clues to understand the immune response observed in COVID-19 patients, which is probably related to viral clearance, but also underlies its pathogenesis and severity. This study associates for the first time COVID-19 severity with an imbalanced humoral immune response characterized by excessive consumption of IgG and C4, identifying new targets for therapeutic intervention.
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- 2020
19. Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19
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Julio Ancochea, Cecilia Muñoz-Calleja, Arantzazu Alfranca, Pedro Landete, Laura Esparcia, Ana Sanchez-Azofra, Ana Alcaraz-Serna, Isidoro González-Álvaro, Joan B. Soriano, Tamara Mateu-Albero, Ana Marcos-Jimenez, Pedro Martínez-Fleta, Ildefonso Sánchez-Cerrillo, Enrique Martin-Gayo, Ignacio Santos, Santiago Sánchez-Alonso, Celia López-Sanz, Ligia Gabrie, Maria J. Calzada, Luciana del Campo Guerola, Elena Ávalos, Francisco Sánchez-Madrid, and Beatriz Aldave
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ARDS ,Lung ,business.industry ,Monocyte ,T cell ,Inflammation ,Dendritic cell ,medicine.disease ,Article ,medicine.anatomical_structure ,Immune system ,Immunology ,medicine ,medicine.symptom ,business ,CD8 - Abstract
The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c+ conventional dendritic cells also followed this pattern, whereas CD141+ conventional and CD123hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.Single-sentence summaryDepletion from the blood and differential activation patterns of inflammatory monocytes and CD1c+ conventional dendritic cells associate with development of ARDS in COVID-19 patients.
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- 2020
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20. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID‐19 patients
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, European Commission, Comunidad de Madrid, Marcos Jiménez, Ana, Sánchez‐Alonso, Santiago, Alcaraz‐Serna, Ana, Esparcia-Pinedo, Laura, López‐Sanz, Celia, Sampedro-Nuñez, Miguel, Mateu‐Albero, Tamara, Sánchez‐Cerrillo, Ildefonso, Martínez‐Fleta, Petra, Gabrie, Ligia, Campo Guerola, Luciana del, Rodríguez-Frade, José Miguel, Casasnovas, José María, Reyburn, H. T., Valés-Gómez, Mar, López Trascasa, Margarita, Martín‐Gayo, Enrique, Calzada, María José, Castañeda, Santos, Fuente, Hortensia de la, González-Álvaro, Isidoro, Sánchez‐Madrid, Francisco, Muñoz‐Calleja, Cecilia, Alfranca, Arántzazu, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, European Commission, Comunidad de Madrid, Marcos Jiménez, Ana, Sánchez‐Alonso, Santiago, Alcaraz‐Serna, Ana, Esparcia-Pinedo, Laura, López‐Sanz, Celia, Sampedro-Nuñez, Miguel, Mateu‐Albero, Tamara, Sánchez‐Cerrillo, Ildefonso, Martínez‐Fleta, Petra, Gabrie, Ligia, Campo Guerola, Luciana del, Rodríguez-Frade, José Miguel, Casasnovas, José María, Reyburn, H. T., Valés-Gómez, Mar, López Trascasa, Margarita, Martín‐Gayo, Enrique, Calzada, María José, Castañeda, Santos, Fuente, Hortensia de la, González-Álvaro, Isidoro, Sánchez‐Madrid, Francisco, Muñoz‐Calleja, Cecilia, and Alfranca, Arántzazu
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SARS‐CoV‐2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID‐19. We investigated whether the specific immune responses in the peripheral blood of 276 patients associated to severity and progression of COVID‐19. At admission, dramatic lymphopenia of T, B and NK cells associated to severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56‐CD16+ NK‐cells increased. Regarding humoral immunity, levels of IgM, IgA and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID‐19 patients, associating severity with an imbalanced humoral response and identifying new targets for therapeutic intervention.
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- 2020
21. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID‐19 patients
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Marcos‐Jiménez, Ana, primary, Sánchez‐Alonso, Santiago, additional, Alcaraz‐Serna, Ana, additional, Esparcia, Laura, additional, López‐Sanz, Celia, additional, Sampedro‐Núñez, Miguel, additional, Mateu‐Albero, Tamara, additional, Sánchez‐Cerrillo, Ildefonso, additional, Martínez‐Fleta, Pedro, additional, Gabrie, Ligia, additional, Campo Guerola, Luciana, additional, Rodríguez‐Frade, José Miguel, additional, Casasnovas, José M., additional, Reyburn, Hugh T., additional, Valés‐Gómez, Mar, additional, López‐Trascasa, Margarita, additional, Martín‐Gayo, Enrique, additional, Calzada, María José, additional, Castañeda, Santos, additional, Fuente, Hortensia, additional, González‐Álvaro, Isidoro, additional, Sánchez‐Madrid, Francisco, additional, Muñoz‐Calleja, Cecilia, additional, and Alfranca, Arantzazu, additional
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- 2021
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22. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study
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Galván-Román, José María, primary, Rodríguez-García, Sebastián C., additional, Roy-Vallejo, Emilia, additional, Marcos-Jiménez, Ana, additional, Sánchez-Alonso, Santiago, additional, Fernández-Díaz, Carlos, additional, Alcaraz-Serna, Ana, additional, Mateu-Albero, Tamara, additional, Rodríguez-Cortes, Pablo, additional, Sánchez-Cerrillo, Ildefonso, additional, Esparcia, Laura, additional, Martínez-Fleta, Pedro, additional, López-Sanz, Celia, additional, Gabrie, Ligia, additional, del Campo Guerola, Luciana, additional, Suárez-Fernández, Carmen, additional, Ancochea, Julio, additional, Canabal, Alfonso, additional, Albert, Patricia, additional, Rodríguez-Serrano, Diego A., additional, Aguilar, Juan Mariano, additional, del Arco, Carmen, additional, de los Santos, Ignacio, additional, García-Fraile, Lucio, additional, de la Cámara, Rafael, additional, Serra, José María, additional, Ramírez, Esther, additional, Alonso, Tamara, additional, Landete, Pedro, additional, Soriano, Joan B., additional, Martín-Gayo, Enrique, additional, Fraile Torres, Arturo, additional, Zurita Cruz, Nelly Daniela, additional, García-Vicuña, Rosario, additional, Cardeñoso, Laura, additional, Sánchez-Madrid, Francisco, additional, Alfranca, Arantzazu, additional, Muñoz-Calleja, Cecilia, additional, González-Álvaro, Isidoro, additional, Alvarado, Teresa, additional, Martínez, Pablo, additional, Javier de la Cuerda Llorente, Francisco, additional, Arco, Carmen del, additional, Villalba, Natalia, additional, Negro, Mónica, additional, Contreras, Elvira, additional, Rey, Ana del, additional, Santiago, Cristina, additional, Junquera, Manuel, additional, Caminero, Raquel, additional, Val, Francisco Javier, additional, González, Sonia, additional, Caño, Marta, additional, López, Isabel, additional, von Wernitz, Andrés, additional, Retana, Bárbara, additional, Guerra, Iñigo, additional, Sorando, Jorge, additional, Chao, Lydia, additional, Cárdenas, María José, additional, Espiga, Verónica, additional, Chicharro, Pablo, additional, Rodríguez, Pedro, additional, Alday, Iñigo Hernando, additional, Sampedro, Miguel, additional, Prada, Jorge, additional, Aldama, Eukene Rojo, additional, Real, Yolanda, additional, Caldas, María, additional, Casabona, Sergio, additional, Lanas-Gimeno, Aitor, additional, Camara, Rafael de la, additional, Alvárez, Angela Figuera, additional, Aguadol, Beatriz, additional, Morell, Alberto, additional, Zurriaga, Amparo Ibáñez, additional, Abanades, María Pérez, additional, García, Silvia Ruiz, additional, Aranda, Tomás Gallego, additional, Ruiz, María, additional, Nieto, Concepción Martínez, additional, Aspa, Javier, additional, Guerola, Luciana del Campo, additional, Fernández, Elena, additional, Calzada, Ma José, additional, Tejedor, Reyes, additional, Iglesias, Judit, additional, Suarez, Fernando, additional, Sánchez, Juan Antonio, additional, Abad, Beatriz, additional, Suarez, Carmen, additional, Santos, Ignacio de los, additional, Galván-Román, José María, additional, Roy, Emilia, additional, Sanz, Jesus, additional, Sanchez, Eduardo, additional, Moldenhauer, Fernando, additional, Casado, Pedro, additional, Curbelo, Jose, additional, Gutierrez, Angela, additional, Bautista, Azucena, additional, Giménez, Nuria Ruiz, additional, Fernandez, Angelica, additional, Parra, Pedro, additional, Moyano, Berta, additional, Barrios, Ana, additional, Real de Asua, Diego, additional, Sanchez, Beatriz, additional, Saez, Carmen, additional, Ciudad, Marianela, additional, Navas, Desiré, additional, Domingo, Laura Cardeñoso, additional, Torresano, María del Carmen Cuevas, additional, García, Diego Domingo, additional, Cavero, Teresa Alarcón, additional, Blanco, Alicia García, additional, Ramírez, Alexandra Martín, additional, Semiglia Chong, María Auxiliadora, additional, Cobos, Ainhoa Gutiérrez, additional, Fraile Torres, Arturo Manuel, additional, Sanchez-Gonzalez, Carmen, additional, Perpén, Antonio Fernádez, additional, Pérez, Carolina Díaz, additional, Soriano, Joan, additional, Cisneros, Carolina, additional, Castillo, Elena García, additional, García Pérez, Francisco Javier, additional, Girón, Rosa María, additional, Marcos, Celeste, additional, Zamora, Enrique, additional, García, Patricia García, additional, Castañeda, Santos, additional, Rodríguez-García, Sebastián, additional, Cubas, Irene Llorente, additional, Tomero, Eva G., additional, Castañeda, Noelia García, additional, Ortiz, Ana Ma, additional, Valero, Cristina, additional, Uriarte, Miren, additional, and Montes, Nuria, additional
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- 2021
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23. Procalcitonina es superior a recuento linfocitario, índice neutrófilo/linfocito y proteína C reactiva para la predicción de mortalidad a 30 días de pacientes con COVID-19 en el servicio de urgencias.
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López-Ayala, Pedro, Alcaraz-Serna, Ana, Valls Carbó, Adrián, Cuadrado Cenzual, Mª Ángeles, Torrejón Martínez, María José, López Picado, Amanda, Martínez Valero, Carmen, Miranda, Juande D., Díaz del Arco, Cristina, Cozar López, Gabriel, Suárez-Cadenas, María del Mar, Jerez Fernández, Pablo, Angós, Beatriz, Rodríguez Adrada, Esther, Cardassay, Eduardo, del Toro, Enrique, Chaparro, David, Montalvo Moraleda, María Teresa, Espejo Paeres, Carolina, and García Briñón, Miguel Ángel
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- 2022
24. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19
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Marcos-Jiménez, Ana, primary, Sánchez-Alonso, Santiago, additional, Alcaraz-Serna, Ana, additional, Esparcia, Laura, additional, López-Sanz, Celia, additional, Sampedro-Núñez, Miguel, additional, Mateu-Albero, Tamara, additional, Sánchez-Cerrillo, Ildefonso, additional, Martínez-Fleta, Pedro, additional, Gabrie, Ligia, additional, del Campo Guerola, Luciana, additional, López-Trascasa, Margarita, additional, Martín-Gayo, Enrique, additional, Calzada, María, additional, Castañeda, Santos, additional, de la Fuente, Hortensia, additional, González-Álvaro, Isidoro, additional, Sánchez-Madrid, Francisco, additional, Muñoz-Calleja, Cecilia, additional, and Alfranca, Arantzazu, additional
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- 2020
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25. Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19
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Sánchez-Cerrillo, Ildefonso, primary, Landete, Pedro, additional, Aldave, Beatriz, additional, Sánchez-Alonso, Santiago, additional, Azofra, Ana Sánchez, additional, Marcos-Jiménez, Ana, additional, Ávalos, Elena, additional, Alcaraz-Serna, Ana, additional, de los Santos, Ignacio, additional, Mateu-Albero, Tamara, additional, Esparcia, Laura, additional, López-Sanz, Celia, additional, Martínez-Fleta, Pedro, additional, Gabrie, Ligia, additional, del Campo Guerola, Luciana, additional, Calzada, María José, additional, González-Álvaro, Isidoro, additional, Alfranca, Arantzazu, additional, Sánchez-Madrid, Francisco, additional, Muñoz-Calleja, Cecilia, additional, Soriano, Joan B, additional, Ancochea, Julio, additional, and Martín-Gayo, Enrique, additional
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- 2020
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26. Aurora A controls CD8+ T cell cytotoxic activity and antiviral response
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Ana Alcaraz-Serna, Salvador Iborra, Marcos Malumbres, José González-Martínez, Noelia Blas-Rus, Eugenio Bustos-Morán, Francisco Sánchez-Madrid, Ministerio de Economía, Industria y Competitividad (España), Comunidad de Madrid (España), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Fundación ProCNIC, Centro de Investigación Biomedica en Red - CIBER, Unión Europea. Comisión Europea, and European Research Council
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Cytotoxicity, Immunologic ,Male ,0301 basic medicine ,T cell ,Receptors, Antigen, T-Cell ,lcsh:Medicine ,Mice, Transgenic ,Vaccinia virus ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Article ,Immunomodulation ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Vaccinia ,medicine ,Animals ,Humans ,Cytotoxic T cell ,lcsh:Science ,Aurora Kinase A ,Multidisciplinary ,Chemistry ,Effector ,lcsh:R ,Degranulation ,3. Good health ,Granzyme B ,Disease Models, Animal ,CTL ,030104 developmental biology ,medicine.anatomical_structure ,Virus Diseases ,Host-Pathogen Interactions ,Cancer research ,lcsh:Q ,030217 neurology & neurosurgery ,CD8 ,Signal Transduction - Abstract
Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4+ T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8+ T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8+ T cells. This finding was similarly proven for both mice and human CD8+ CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8+ T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats. This study was supported by grants SAF2017/82886-R and BIO2012-37926 from the Spanish Ministry of Economy and Competitiveness, INFLAMUNE-CAMS2017/BMD-3671 from the Comunidad de Madrid and ERC-2011-AdG 294340-GENTRIS. Red Cardiovascular RD 12-0042-0056 from Instituto Salud Carlos III (ISCIII) and also CIBER Cardiovascular. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and it is a Severo Ochoa Centre of Excellence (SEV-2015-0505). Sí
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- 2019
27. Extracellular Vesicle-Mediated Immune Regulation of Tissue Remodeling and Angiogenesis After Myocardial Infarction
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Sánchez-Alonso, Santiago, primary, Alcaraz-Serna, Ana, additional, Sánchez-Madrid, Francisco, additional, and Alfranca, Arantzazu, additional
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- 2018
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28. Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets
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Cuesta-Mateos, Carlos, primary, Alcaraz-Serna, Ana, additional, Somovilla-Crespo, Beatriz, additional, and Muñoz-Calleja, Cecilia, additional
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- 2018
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29. Aurora A controls CD8+ T cell cytotoxic activity and antiviral response.
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Bustos-Morán, Eugenio, Blas-Rus, Noelia, Alcaraz-Serna, Ana, Iborra, Salvador, González-Martínez, José, Malumbres, Marcos, and Sánchez-Madrid, Francisco
- Abstract
Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4
+ T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8+ T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8+ T cells. This finding was similarly proven for both mice and human CD8+ CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8+ T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats. [ABSTRACT FROM AUTHOR]- Published
- 2019
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30. [CAR-T therapy for autoimmune diseases].
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Alcaraz-Serna A, Porret R, Trueb L, Ribi C, Seebach J, and Muller YD
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- Humans, Immunotherapy, Adoptive, Cell- and Tissue-Based Therapy, Pathologic Complete Response, Receptors, Chimeric Antigen, Autoimmune Diseases therapy
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Cellular therapy using genetically modified T lymphocytes expressing synthetic receptors, known as CAR (Chimeric Antigen Receptor), has revolutionized the treatment of certain hematologic malignancies. This success has led to exploring the same approach in the treatment of severe autoimmune diseases refractory to conventional therapies. Initial results in systemic lupus erythematosus have shown complete remissions that appear to persist over time. Consequently, there is a growing number of ongoing clinical trials. In this review, we discuss the rationale behind the use of CAR-T therapies, the targeted autoimmune diseases, and the associated risks., Competing Interests: Le Pr Y. D. Müller est inventeur d’une licence sur les CAR-T (US 2023/0340068 A1) et responsable de site d’une étude CAR-T (NCT05798117). Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.
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- 2024
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31. Procalcitonin concentration in the emergency department predicts 30-day mortality in COVID-19 better than the lymphocyte count, the neutrophil-tolymphocyte ratio, or the C-reactive protein level.
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López-Ayala P, Alcaraz-Serna A, Valls Carbó A, Cuadrado Cenzual MÁ, Torrejón Martínez MJ, López Picado A, Martínez Valero C, Miranda JD, Díaz Del Arco C, Cozar López G, Suárez-Cadenas MDM, Jerez Fernández P, Angós B, Rodríguez Adrada E, Cardassay E, Del Toro E, Chaparro D, Montalvo Moraleda MT, Espejo Paeres C, García Briñón MÁ, Hernández Martín-Romo V, Ortega L, Fernández Pérez C, Martínez-Novillo M, González Armengol JJ, González Del Castillo J, Mueller CE, and Martín-Sánchez FJ
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- Aged, C-Reactive Protein analysis, Calcitonin, Emergency Service, Hospital, Humans, Lymphocyte Count, Male, Middle Aged, Neutrophils chemistry, Retrospective Studies, COVID-19 diagnosis, Procalcitonin
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Objectives: Although many demographic and clinical predictors of mortality have been studied in relation to COVID-19, little has been reported about the prognostic utility of inflammatory biomarkers., Material and Methods: Retrospective cohort study. All patients with laboratory-confirmed COVID-19 treated in a hospital emergency department were included consecutively if baseline measurements of the following biomarkers were on record: lymphocyte counts, neutrophil-to-lymphocyte ratio NRL, and C-reactive protein (CRP) and procalcitonin (PCT) levels. We analyzed associations between the biomarkers and all-cause 30-day mortality using Cox regression models and dose-response curves., Results: We included 896 patients, 151 (17%) of whom died within 30 days. The median (interquartile range) age was 63 (51-78) years, and 494 (55%) were men. NLR, CRP and PCT levels at ED presentation were higher, while lymphocyte counts were lower, in patients who died compared to those who survived (P .001). The areas under the receiver operating characteristic curves revealed the PCT concentration (0.79; 95% CI, 0.75-0.83) to be a better predictor of 30-day mortality than the lymphocyte count (0.70; 95% CI, 0.65-0.74; P .001), the NLR (0.74; 95% CI, 0.69-0.78; P = .03), or the CRP level (0.72; 95% CI, 0.68-0.76; P .001). The proposed PCT concentration decision points for use in emergency department case management were 0.06 ng/L (negative) and 0.72 ng/L (positive). These cutoffs helped classify risk in 357 patients (40%). Multivariable analysis demonstrated that the PCT concentration had the strongest association with mortality., Conclusion: PCT concentration in the emergency department predicts all-cause 30-day mortality in patients with COVID-19 better than other inflammatory biomarkers.
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- 2022
32. Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19.
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Sanchez-Cerrillo I, Landete P, Aldave B, Sanchez-Alonso S, Sanchez-Azofra A, Marcos-Jimenez A, Avalos E, Alcaraz-Serna A, de Los Santos I, Mateu-Albero T, Esparcia L, Lopez-Sanz C, Martinez-Fleta P, Gabrie L, Del Campo Guerola L, Calzada MJ, Gonzalez-Alvaro I, Alfranca A, Sanchez-Madrid F, Munoz-Calleja C, Soriano JB, Ancochea J, and Martin-Gayo E
- Abstract
The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c+ conventional dendritic cells also followed this pattern, whereas CD141+ conventional and CD123hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.
- Published
- 2020
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