8 results on '"Costa, Carme"'
Search Results
2. Inhibition of the BMP Signaling Pathway Ameliorated Established Clinical Symptoms of Experimental Autoimmune Encephalomyelitis
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Eixarch, Herena, Calvo-Barreiro, Laura, Costa, Carme, Reverter-Vives, Gemma, Castillo, Mireia, Gil, Vanessa, Del Río, José Antonio, Montalban, Xavier, and Espejo, Carmen
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- 2020
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3. Semaphorin 7A as a Potential Therapeutic Target for Multiple Sclerosis
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Gutiérrez-Franco, Ana, Eixarch, Herena, Costa, Carme, Gil, Vanessa, Castillo, Mireia, Calvo-Barreiro, Laura, Montalban, Xavier, Del Río, José A., and Espejo, Carmen
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- 2017
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4. CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS
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Fissolo, Nicolás, Matute-Blanch, Clara, Osman, Mohamoud, Costa, Carme, Pinteac, Rucsanda, Miró, Berta, Sanchez, Alex, Brito, Verónica, Dujmovic, Irena, Voortman, Margarete, Khalil, Michael, Borràs, Eva, Sabidó, Eduard, Issazadeh-Navikas, Shohreh, Montalban, Xavier, Comabella, Manuel, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Fissolo N, Matute-Blanch C, Costa C, Pinteac R, Brito V, Comabella Lopez M] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Osman M] Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Denmark. [Miró B] Unitat d'Estadística i Bioinformàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Sanchez A] Unitat d'Estadística i Bioinformàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Genetics, Microbiology and Statistics Department, Universitat de Barcelona, Spain. [Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Center for Multiple Sclerosis, St. Michael’s Hospital, University of Toronto, ON, Canada, and Vall d'Hebron Barcelona Hospital Campus
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Male ,0301 basic medicine ,Enzims proteolítics - Inhibidors ,enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple::esclerosis múltiple crónica progresiva [ENFERMEDADES] ,Esclerosi múltiple ,Gastroenterology ,factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS] ,Cohort Studies ,Mice ,0302 clinical medicine ,Esclerosi múltiple - Diagnòstic ,aminoácidos, péptidos y proteínas::péptidos::serpinas [COMPUESTOS QUÍMICOS Y DROGAS] ,biology ,medicine.diagnostic_test ,Biochemical markers ,Experimental autoimmune encephalomyelitis ,Animal models in research ,Enzyme inhibitors ,Middle Aged ,Multiple Sclerosis, Chronic Progressive ,Neural stem cell ,Cerebrospinal fluid ,Neurology ,Marcadors bioquímics ,Biomarker (medicine) ,Female ,Adult ,medicine.medical_specialty ,Encephalomyelitis, Autoimmune, Experimental ,Immunofluorescence ,Biological Factors::Biomarkers [CHEMICALS AND DRUGS] ,Neuroprotection ,Article ,Multiple sclerosis ,03 medical and health sciences ,Downregulation and upregulation ,030225 pediatrics ,Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis::Multiple Sclerosis, Chronic Progressive [DISEASES] ,Internal medicine ,medicine ,Animals ,Humans ,In patient ,Serpins ,Serine protease ,business.industry ,Líquid cefalorraquidi ,Correction ,medicine.disease ,Amino Acids, Peptides, and Proteins::Peptides::Serpins [CHEMICALS AND DRUGS] ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Inhibidors enzimàtics ,biology.protein ,Neurology (clinical) ,Models animals en la investigació ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Multiple sclerosis; SERPINA3 Esclerosi múltiple; SERPINA3 Esclerosis múltiple; SERPINA3 Objective To identify biomarkers associated with progressive phases of MS and with neuroprotective potential. Methods Combined analysis of the transcriptional and proteomic profiles obtained in CNS tissue during chronic progressive phases of experimental autoimmune encephalomyelitis (EAE) with the transcriptional profile obtained during the differentiation of murine neural stem cells into neurons. Candidate biomarkers were measured by ELISA in the CSF of 65 patients with MS (29 with relapsing-remitting MS [RRMS], 20 with secondary progressive MS, and 16 with primary progressive MS [PPMS]) and 30 noninflammatory neurologic controls (NINCs). Results Integrative analysis of gene and protein expression data identified 2 biomarkers, the serine protease inhibitor Serpina3n and the calcium-binding protein S100A4, which were upregulated in chronic progressive EAE and whose expression was induced during neuronal differentiation. Immunofluorescence studies revealed a primarily neuronal expression of S100A4 and Serpina3n during EAE. CSF levels of SERPINA3, the human ortholog of murine Serpina3n, and S100A4 were increased in patients with MS compared with NINCs (SERPINA3: 1,320 vs 838.6 ng/mL, p = 0.0001; S100A4: 1.6 vs 0.8 ng/mL, p = 0.02). Within the MS group, CSF SERPINA3 levels were significantly elevated in patients with progressive forms, mainly patients with PPMS compared with patients with RRMS (1,617 vs 1,129 ng/mL, p = 0.02) and NINCs (1,617 vs 838.6 ng/mL, p = 0.0001). Of interest, CSF SERPINA3 levels significantly correlated with CSF neurofilament light chain levels only in the PPMS group (r = 0.62, p = 0.01). Conclusion These results point to a role of SERPINA3 as a biomarker associated with the progressive forms of MS, particularly PPMS. This work was supported by grants from the Fondo de Investigación Sanitaria (FIS; grant number PI17/00596), Ministry of Science and Innovation, Spain; Generalitat de Catalunya Suport Grups de Recerca (2017 SGR 0527); and the Red Española de Esclerosis Múltiple (RD16/0015/0004) funded by the FIS.
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- 2021
5. Circulating EZH2-positive T cells are decreased in multiple sclerosis patients
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Malhotra, Sunny, Villar, Luisa M., Costa, Carme, Midaglia, Luciana, Cubedo, Marta, Medina, Silvia, Fissolo, Nicolás, Río, Jordi, Castilló, Joaquín, Álvarez-Cermeño, José C., Sánchez, Alex, Montalban, Xavier, Comabella, Manuel, Universitat Autònoma de Barcelona, and Universitat de Barcelona
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0301 basic medicine ,Male ,Talin ,Freund's Adjuvant ,Esclerosi múltiple ,Encefalomielitis ,lcsh:RC346-429 ,Cohort Studies ,Mice ,0302 clinical medicine ,Immunophenotyping ,T-Lymphocyte Subsets ,Encephalomyelitis ,Migration ,Chemistry ,Cell adhesion molecule ,General Neuroscience ,Experimental autoimmune encephalomyelitis ,Middle Aged ,Multiple Sclerosis, Chronic Progressive ,medicine.anatomical_structure ,Neurology ,Cèl·lules T ,Cytokines ,Female ,Adult ,Encephalomyelitis, Autoimmune, Experimental ,T cell ,Immunology ,T cells ,macromolecular substances ,Peripheral blood mononuclear cell ,Multiple sclerosis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Young Adult ,Multiple Sclerosis, Relapsing-Remitting ,medicine ,Animals ,Humans ,Enhancer of Zeste Homolog 2 Protein ,EZH2 ,Cell adhesion ,Proto-Oncogene Proteins c-vav ,lcsh:Neurology. Diseases of the nervous system ,Research ,medicine.disease ,Molecular biology ,Peptide Fragments ,Mice, Inbred C57BL ,Treatment ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,Leukocytes, Mononuclear ,Myelin-Oligodendrocyte Glycoprotein ,Adhesion molecules ,030217 neurology & neurosurgery ,CD8 - Abstract
Background Recent studies in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), suggest an involvement of the histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in important processes such as cell adhesion and migration. Methods Here, we aimed to expand these initial observations by investigating the role of EZH2 in MS. mRNA expression levels for EZH2 were measured by real-time PCR in peripheral blood mononuclear cells (PBMC) from 121 MS patients (62 untreated and 59 receiving treatment) and 24 healthy controls. Results EZH2 expression levels were decreased in PBMC from untreated patients compared to that from controls, and treatment significantly upregulated EZH2 expression. Expression of miR-124 was increased in MS patients compared to controls. Blood immunophenotyping revealed EZH2 expression mostly restricted to CD4+ and CD8+ T cells, and circulating EZH2+ CD4+ and CD8+ T cells were decreased in untreated MS patients compared to controls. CD8+ T cells expressing EZH2 exhibited a predominant central memory phenotype, whereas EZH2+ CD4+ T cells were of effector memory nature, and both T cell subsets produced TNF-α. EZH2+ T cells were enriched in the cerebrospinal fluid compartment compared to blood and were found in chronic active lesions from MS patients. EZH2 inhibition and microarray analysis in PBMC was associated with significant downregulation of key T cell adhesion molecules. Conclusion These findings suggest a role of EZH2 in the migration of T cells in MS patients. The observation of TNF-α expression by CD4+ and CD8+ T cells expressing EZH2 warrants additional studies to explore more in depth the pathogenic potential of EZH2+-positive cells in MS. Electronic supplementary material The online version of this article (10.1186/s12974-018-1336-9) contains supplementary material, which is available to authorized users.
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- 2018
6. Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
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Miralles, Marta, Eixarch, Herena, Tejero Ambrosio, Marcos, Costa, Carme, Hirota, Keiji, Castaño, A. Raul, Puig Ferrer, Meritxell, Stockinger, Gitta, Montalban, Xavier, Bosch i Merino, Assumpció, Espejo, Carmen, Chillón Rodríguez, Miguel, Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular, and Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia
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0301 basic medicine ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Genetic Vectors ,Biology ,Multiple sclerosis ,03 medical and health sciences ,Myelin ,0302 clinical medicine ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Pharmacology ,Microglia ,EAE ,Experimental autoimmune encephalomyelitis ,Interleukin ,Genetic Therapy ,Receptors, Interleukin ,Dependovirus ,Myelitis ,medicine.disease ,Oligodendrocyte ,Mice, Inbred C57BL ,AAV vector ,030104 developmental biology ,medicine.anatomical_structure ,HEK293 Cells ,Spinal Cord ,Astrocytes ,Immunology ,STAT protein ,Th17 Cells ,Cytokine secretion ,Female ,Original Article ,Neurology (clinical) ,Th17 ,IL-23R ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
The role of the T helper (Th)17 pathway has been clearly demonstrated in the onset and progression of autoimmune diseases, where interleukin (IL)-23 is a key molecule in maintaining the response mediated by Th17 cells. As a consequence, recent strategies based on blocking the interaction between IL-23 and its receptor (IL-23R), for example the anti-p19 antibody tildrakizumab, have been developed to regulate the Th17 pathway from the initial stages of the disease. Here, a soluble (s)IL-23R cDNA was cloned in expression plasmids and viral vectors. The clinical efficacy of sIL-23R was evaluated in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis mice intravenously injected with a single dose of adeno-associated virus AAV8–sIL-23R vectors. Cytokine secretion was determined by multiplex assay, while histopathological analysis of the central nervous system was performed to study demyelination, inflammatory infiltration, and microglia and astroglia activation. We observed that administration of adeno-associated vector 8 encoding sIL-23R was associated with a significant disease improvement, including delay in the onset of the clinical signs; slower progress of the disease; interference with IL-23-mediated signal transducer and activator of transcription response by inhibiting of signal transducer and activator of transcription 3 phosphorylation; reduced demyelination and infiltration in the central nervous system; and lower astrocyte and microglia activation. Our results suggest that the use of vectors carrying sIL-23R to block the IL-23/IL-23R interaction may be a new therapeutic strategy for the treatment of multiple sclerosis. Electronic supplementary material The online version of this article (doi:10.1007/s13311-017-0545-8) contains supplementary material, which is available to authorized users.
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- 2017
7. Myeloid-derived suppressor cells expressing a self-antigen ameliorate experimental autoimmune encephalomyelitis.
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Casacuberta-Serra, Silvia, Costa, Carme, Eixarch, Herena, Mansilla, María José, López-Estévez, Sergio, Martorell, Lluís, Parés, Marta, Montalban, Xavier, Espejo, Carmen, and Barquinero, Jordi
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MYELOID leukemia , *SUPPRESSOR cells , *ANTIGEN receptors , *ENCEPHALOMYELITIS , *BONE marrow cells - Abstract
Previous work by our group showed that transferring bone marrow cells transduced with a self-antigen induced immune tolerance and ameliorated experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We also found that following retroviral transduction of murine bone marrow (BM) cells, the majority of cells generated and transduced were myeloid-derived suppressor cells (MDSCs). Here, we aimed to determine whether purified antigen-expressing MDSCs have similar therapeutic effects than those of unfractionated BM, and to investigate their potential mechanisms. We performed phenotypic and functional analyses in these cells using the same animal model, and we used purified antigen-expressing MDSCs in preventive and therapeutic approaches. These cells exerted therapeutic effects similar to those of BM cells, which depended upon self-antigen expression. The majority of monocytic (M)-MDSCs expressed the immunosuppressive molecule programmed death ligand-1 (PD-L1), CD80, CD86 and MHC class II molecules. Additionally, the animals infused with antigen-expressing cells exhibited lower percentages of activated T cells and higher percentages of B cells with a regulatory phenotype (B220 + CD1d high CD5 + ) in the spleen than their respective controls. MDSCs expressing self-antigens, alloantigens or therapeutic transgenes are tolerogenic and can be exploited therapeutically in autoimmune diseases, transplantation and in gene therapy, respectively. [ABSTRACT FROM AUTHOR]
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- 2016
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8. Differential expression of sema3A and sema7A in a murine model of multiple sclerosis: Implications for a therapeutic design.
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Gutiérrez-Franco, Ana, Costa, Carme, Eixarch, Herena, Castillo, Mireia, Medina-Rodríguez, Eva M., Bribián, Ana, de Castro, Fernando, Montalban, Xavier, and Espejo, Carmen
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SEMAPHORINS , *MULTIPLE sclerosis , *THERAPEUTICS , *ENCEPHALOMYELITIS , *NEURODEGENERATION - Abstract
We characterised the expression of semaphorin (sema)3A, sema7A and their receptors in the immune and the central nervous system (CNS) at different stages of experimental autoimmune encephalomyelitis (EAE). We also studied their expression in neonatal and adult oligodendrocyte progenitor cell (OPC) and in mature oligodendrocyte cultures. Our results show that sema3A is increased in the CNS and decreased in the immune system upon EAE induction. However, sema7A expression is increased in both the CNS and the immune system during EAE. We also detected sema3A, sema7A and their receptors in neonatal and adult OPCs and in mature oligodendrocytes. These data suggest that sema3A and sema7A are involved in the pathogenesis of EAE, in the modulation of the immune response and in the neurodegeneration that take place in the CNS. Sema7A may represent an intriguing potential therapeutic target for the treatment of both the neurodegenerative and immune-mediated disease processes in MS. [ABSTRACT FROM AUTHOR]
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- 2016
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