المؤلفون: Saiz Hinarejos, Albert

المساهمون: University/Department: Universitat de Barcelona. Departament de Medicina

مرشدي الرسالة: Tolosa, Eduardo

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: Neurotransmissió, Enzims, Malalties del sistema nerviós, Ciències de la Salut

الوصف: El GAD (glutamato decarboxilasa) es la enzima que cataliza la síntesis del neurotransmisor inhibitorio ácido gamma-aminobutírico (GABA) a partir del glutamato. El GAD se expresa selectivamente en los botones sinápticos de las neuronas GABA-érgicas. Fuera del sistema nervioso se encuentra en altas concentraciones en las células beta de los islotes pancreáticos, sin que existan diferencias entre el GAD de las células pancreáticas o del sistema nervioso.La repuesta inmune contra el GAD se ha relacionado con la patogenia de dos enfermedades humanas: el síndrome de la persona rígida ("Stiff-Person syndrome", SPR) y la diabetes mellitas insulino-dependiente (DMID). Alrededor del 80% de los pacientes con DMID recientemente diagnosticada presentan anticuerpos anti-GAD (Ac-GAD) y éstos pueden ser detectados años antes del inicio de la clínica, de manera que los Ac-GAD constituyen un marcador serológico precoz y altamente predictivo de un futuro desarrollo de DMID en sujetos no diabéticos. Por otra parte, el síndrome de la persona rígida (SPR) es un raro trastorno del sistema nervioso central caracterizado por rigidez muscular progresiva asociado a espasmos dolorosos. En este caso, los Ac-GAD son detectados aproximadamente en el 60% de los pacientes con SPR. El papel patogénico directo de los Ac-GAD en el SPR es objeto de controversia porque el GAD es un antígeno citoplasmático no expuesto al medio extracelular. Se ha propuesto que la respuesta autoinmune anti-GAD es un epifenómeno relacionado con la destrucción celular y la exposición de este antígeno, pero su ausencia en la mayoría de cuadros de otras enfermedades degenerativas lo hace improbable. En consecuencia, el objetivo principal de la presente tesis es evaluar la frecuencia de Ac-GAD en enfermedades neurológicas en las que existe una disfunción GABA-érgica conocida. Su evaluación permitirá dar respuesta a si la autoinmunidad anti-GAD es un epifenómeno, y si existe algún otro subgrupo de pacientes con características inmunológicas similar al del SPR, pero con presentación clínica diferente. La caracterización del perfil clínico e inmunológico de este subgrupo de pacientes es el segundo objetivo propuesto en este estudio.

وصف الملف: application/pdf

الوصول الحر: http://www.tdx.cat/TDX-0527108-112853Test
http://hdl.handle.net/10803/2235Test

المؤلفون: Casas Roma, Jordi, Martinez-Heras, Eloy, Solé Ribalta, Albert, Solana, Elisabeth, López Soley, Elisabet, Vivó Sánchez, Francisco Javier, Diaz Hurtado, Marcos, Alba Arbalat, Salut, Sepúlveda, Maria, Blanco, Yolanda, Saiz Hinarejos, Albert, Borge Holthoefer, Javier, Llufriu, Sara, Prados, Ferran

المساهمون: Universitat Politècnica de Catalunya. Departament d'Òptica i Optometria

مصطلحات موضوعية: Àrees temàtiques de la UPC::Ciències de la salut::Medicina, Multiple sclerosis, Magnetic resonance, Central nervous system, Structural connectivity, Functional connectivity, Gray matter networks, Multilayer, Esclerosi múltiple, Ressonància magnètica, Sistema nerviós central

الوصف: In recent years, research on network analysis applied to MRI data has advanced significantly. However, the majority of the studies are limited to single networks obtained from resting-state fMRI, diffusion MRI, or gray matter probability maps derived from T1 images. Although a limited number of previous studies have combined two of these networks, none have introduced a framework to combine morphological, structural, and functional brain connectivity networks. The aim of this study was to combine the morphological, structural, and functional information, thus defining a new multilayer network perspective. This has proved advantageous when jointly analyzing multiple types of relational data from the same objects simultaneously using graph- mining techniques. The main contribution of this research is the design, development, and validation of a framework that merges these three layers of information into one multilayer network that links and relates the integrity of white matter connections with gray matter probability maps and resting-state fMRI. To validate our framework, several metrics from graph theory are expanded and adapted to our specific domain characteristics. This proof of concept was applied to a cohort of people with multiple sclerosis, and results show that several brain regions with a synchronized connectivity deterioration could be identified. ; Peer Reviewed ; Postprint (published version)

وصف الملف: 18 p.; application/pdf

العلاقة: https://direct.mit.edu/netn/article/6/3/916/111665/Applying-multilayer-analysis-to-morphologicalTest; Casas, J. [et al.]. Applying multilayer analysis to morphological, structural, and functional brain networks to identify relevant dysfunction patterns. "Network neuroscience", 1 Juliol 2022, vol. 6, núm. 3, p. 916-933.; http://hdl.handle.net/2117/401765Test

الإتاحة: https://doi.org/10.1162/netn_a_00258Test
http://hdl.handle.net/2117/401765Test

المؤلفون: Guasp, Mar, Muñoz Sánchez, Guillermo, Martínez Hernández, Eugenia, Santana, Daniel, Carbayo, Álvaro, Naranjo, Laura, Bolós, Uma, Framil, Mario, Saiz Hinarejos, Albert, Balasa, Mircea, Ruiz García, Raquel, Sánchez Valle, Raquel, Barcelona Neuro-COVID Study Group

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

مصطلحات موضوعية: COVID-19, Encefalitis, Encephalitis

الوصف: Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months. We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other. Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement. In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process.

وصف الملف: 10 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.866153Test; Frontiers in Immunology, 2022, vol. 13; https://doi.org/10.3389/fimmu.2022.866153Test; http://hdl.handle.net/2445/185909Test; 9308286

الإتاحة: https://doi.org/10.3389/fimmu.2022.866153Test
http://hdl.handle.net/2445/185909Test

المؤلفون: Fernández Velasco, José I., Monreal, Enric, Kuhle, Jens, Meca Lallana, Virginia, Meca Lallana, José E., Izquierdo, Guillermo, Oreja Guevara, Celia, Gascón Gimenez, Francisco, Sainz de la Maza, Susana, Walo Delgado, Paulette E., Lapuente Suanzes, Paloma, Maceski, Aleksandra, Rodriguez Martín, Eulalia, Roldán, Ernesto, Villarrubia, Noelia, Saiz Hinarejos, Albert, Blanco, Yolanda, Diaz Pérez, Carolina, Valero López, Gabriel, Díaz Díaz, Judit, Aladro, Yolanda, Brieva, Luis, Iñíguez, Cristina, González Suárez, Inés, Rodríguez de Antonio, Luis A., García Domínguez, José M., Sabin, Julia, Llufriu Duran, Sara, Masjuan, Jaime, Costa Frossard, Lucienne, Villar, Luisa M.

المصدر: Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

مصطلحات موضوعية: Esclerosi múltiple, Imatges per ressonància magnètica, Multiple sclerosis, Magnetic resonance imaging

الوصف: To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula.More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels.Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.Copyright © 2022 Fernández-Velasco, Monreal, Kuhle, Meca-Lallana, Meca-Lallana, Izquierdo, Oreja-Guevara, Gascón-Giménez, Sainz de la Maza, Walo-Delgado, Lapuente-Suanzes, Maceski, Rodríguez-Martín, Roldán, Villarrubia, Saiz, Blanco, Diaz-Pérez, Valero-López, Diaz-Diaz, Aladro, Brieva, Íñiguez, González-Suárez, Rodríguez de Antonio, García-Domínguez, Sabin, Llufriu, Masjuan, Costa-Frossard and Villar.

وصف الملف: 12 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.842354Test; Frontiers In Immunology, 2022, vol. 13; https://doi.org/10.3389/fimmu.2022.842354Test; http://hdl.handle.net/2445/201067Test; 9306915

الإتاحة: https://doi.org/10.3389/fimmu.2022.842354Test
http://hdl.handle.net/2445/201067Test

المؤلفون: Alba Arbalat, Salut, Andorra, Magi, Sánchez Dalmau, Bernardo, Camos Carreras, Anna, Dotti Boada, Marina, Pulido-Valdeolivas, Irene, Llufriu, Sara, Blanco, Yolanda, Sepúlveda, Maria, Saiz Hinarejos, Albert, Batet Torrell, Óscar, Bilbao, Iker, Torre, Iratxe, Amat Roldán, Iván, Martínez Lapiscina, Elena H., Villoslada, Pablo

المساهمون: Universitat Politècnica de Catalunya. Departament d'Òptica i Optometria

مصطلحات موضوعية: Àrees temàtiques de la UPC::Ciències de la visió, Àrees temàtiques de la UPC::Ciències de la salut::Medicina, Multiple sclerosis, Retina, Raman spectroscopy, Molecular imaging, Esclerosi múltiple, Espectroscòpia Raman

الوصف: Purpose: Raman spectroscopy allows molecular changes to be quantified in vivo from the tissues like the retina. Here we aimed to assess the metabolic changes in the retina of patients with multiple sclerosis (MS). Methods: We built a Raman spectroscopy prototype by connecting a scanning laser ophthalmoscope to a spectrophotometer. We defined the spectra of 10 molecules participating on energy supply, axon biology, or synaptic damage, which have been shown to be altered in the brain of patients with MS: cytochrome C, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NADH), N-acetyl-aspartate (NAA), excitotoxicity, glutamate, amyloid ß (Aß), t and a-synuclein (SNCA), phosphatidyl-ethanolamine, and phosphatidyl-choline. We studied these molecules in a prospective cohort of patients with MS, either in the chronic phase or during relapses of acute optic neuritis (AON). Results: Significant changes to all these molecules were associated with age in healthy individuals. There was a significant decrease in NADH and a trend toward a decrease in NAA in patients with MS, as well as an increase in Aß compared with healthy controls. Moreover, NADH and FAD increased over time in a longitudinal analysis of patients with MS, whereas Aß diminished. In patients with acute retinal inflammation due to AON, there was a significant increase in FAD and a decrease in SNCA in the affected retina. Moreover, glutamate levels increased in the affected eyes after a 6-month follow-up. Conclusions: Alterations of molecules related to axonal degeneration are observed during neuroinflammation and show dynamic changes over time, suggesting progressive neurodegeneration. ; Peer Reviewed ; Postprint (published version)

وصف الملف: application/pdf

العلاقة: https://iovs.arvojournals.org/article.aspx?articleid=2772587Test; Alba-Arbalat, S. [et al.]. In vivo molecular changes in the retina of patients with multiple sclerosis. "Investigative ophthalmology & visual science", 11 Maig 2021, vol. 62, núm. 6, article 11.; http://hdl.handle.net/2117/401771Test

الإتاحة: https://doi.org/10.1167/iovs.62.6.11Test
http://hdl.handle.net/2117/401771Test

المؤلفون: López Soley, Elisabet, Martinez-Heras, Eloy, Andorra, Magi, Solanes Font, Aleix, Radua, Joaquim, Montejo, Carmen, Alba Arbalat, Salut, Sola Valls, Núria, Pulido-Valdeolivas, Irene, Sepúlveda, Maria, Romero Pinel, Lucia, Munteis Olivas, Elvira, Martínez Rodríguez, Jose Enrique, Blanco, Yolanda, Martínez Lapiscina, Elena H., Villoslada, Pablo, Saiz Hinarejos, Albert, Solana, Elisabeth, Llufriu, Sara

المساهمون: Universitat Politècnica de Catalunya. Departament d'Òptica i Optometria

مصطلحات موضوعية: Àrees temàtiques de la UPC::Ciències de la salut::Medicina, Multiple sclerosis, Cognitive neuroscience, Cognition, Cognitive impairment, Neuroimaging, Longitudinal, Predictors, Esclerosi múltiple, Neurociència cognitiva, Cognició

الوصف: Background: The evolution and predictors of cognitive impairment (CI) in multiple sclerosis (MS) are poorly understood. We aimed to define the temporal dynamics of cognition throughout the disease course and identify clinical and neuroimaging measures that predict CI. (2) Methods: This paper features a longitudinal study with 212 patients who underwent several cognitive examinations at different time points. Dynamics of cognition were assessed using mixed-effects linear spline models. Machine learning techniques were used to identify which baseline demographic, clinical, and neuroimaging measures best predicted CI. (3) Results: In the first 5 years of MS, we detected an increase in the z-scores of global cognition, verbal memory, and information processing speed, which was followed by a decline in global cognition and memory (p < 0.05) between years 5 and 15. From 15 to 30 years of disease onset, cognitive decline continued, affecting global cognition and verbal memory. The baseline measures that best predicted CI were education, disease severity, lesion burden, and hippocampus and anterior cingulate cortex volume. (4) Conclusions: In MS, cognition deteriorates 5 years after disease onset, declining steadily over the next 25 years and more markedly affecting verbal memory. Education, disease severity, lesion burden, and volume of limbic structures predict future CI and may be helpful when identifying at-risk patients. ; The author(s) disclose receipt of the following financial support for the research, authorship, and/or publication of this article. This work was funded by: a Proyecto de Investigación en Salud (PI15/00587 to S.LL., and A.S.; PI15/00061 to P.V.; PI18/01030 to S.LL. and A.S.; and JR16/00006; MV17/00021; PI17/01228; RD16/0015/0003 to E.H.M-L.), integrated into the Plan Estatal de Investigación Científica y Técnica de Innovación I+D+I, and co-funded by the Instituto de Salud Carlos III-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER, “Otra manera de hacer ...

وصف الملف: application/pdf

العلاقة: https://www.mdpi.com/2075-4426/11/11/1107Test; López, E. [et al.]. Dynamics and predictors of cognitive impairment along the disease course in multiple sclerosis. "Journal of personalized medicine", 28 Octubre 2021, vol. 11, núm. 11.; http://hdl.handle.net/2117/401744Test

الإتاحة: https://doi.org/10.3390/jpm11111107Test
http://hdl.handle.net/2117/401744Test

المؤلفون: Ruiz García, Raquel, Muñoz Sánchez, Guillermo, Naranjo, Laura, Guasp, Mar, Sabater, Lidia, Saiz Hinarejos, Albert, Dalmau Obrador, Josep, Graus Ribas, Francesc, Martinez Hernandez, Eugenia

المصدر: Articles publicats en revistes (Medicina)

مصطلحات موضوعية: Encefalitis, Immunohistoquímica, Malalties autoimmunitàries, Encephalitis, Immunohistochemistry, Autoimmune diseases

الوصف: Detection of neuronal surface antibodies (NSAb) is important for the diagnosis of autoimmune encephalitis (AE). Although most clinical laboratories use a commercial diagnostic kit (Euroimmun, Lübeck, Germany) based on indirect immunofluorescence on transfected cells (IIFA), clinical experience suggests diagnostic limitations. Here, we assessed the performance of the commercial IIFA in serum and CSF samples of patients with suspected AE previously examined by rat brain immunohistochemistry (Cohort A). Of 6213 samples, 404 (6.5%) showed brain immunostaining suggestive of NSAb: 163 (40%) were positive by commercial IIFA and 241 (60%) were negative. When these 241 samples were re-assessed with in-house IIFA, 42 (18%) were positive: 21 (9%) had NSAb against antigens not included in the commercial IIFA and the other 21 (9%) had NSAb against antigens included in the commercial kit (false negative results). False negative results occurred more frequently with CSF (29% vs 10% in serum) and predominantly affected GABABR (39%), LGI1 (17%) and AMPAR (11%) antibodies. Results were reproduced in a separate cohort (B) of 54 AE patients with LGI1, GABABR or AMPAR antibodies in CSF which were missed in 30% by commercial IIFA. Patients with discordant GABABR antibody results (positive in-house but negative commercial IIFA) were less likely to develop full-blown clinical syndrome; no significant clinical differences were noted for the other antibodies. Overall, NSAb testing by commercial IIFA led to false negative results in a substantial number of patients, mainly those affected by anti-LG1, GABABR or AMPAR encephalitis. If these disorders are suspected and commercial IIFA is negative, more comprehensive antibody studies are recommended

وصف الملف: 8 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2021.691536Test; Frontiers in Immunology, 2021, vol. 12, num. 691536; https://doi.org/10.3389/fimmu.2021.691536Test; http://hdl.handle.net/2445/184018Test; 720213; 9272815

الإتاحة: https://doi.org/10.3389/fimmu.2021.691536Test
http://hdl.handle.net/2445/184018Test

المؤلفون: Landa, Jon, Guasp, Mar, Miguez Cabello, Federico, Guimarães, Joana, Mishima, Takayasu, Oda, Fumiko, Zipp, Frauke, Krajinovic, Vladimir, Fuhr, Peter, Honnorat, Jerome, Titulaer, Maarten J., Simabukuro, Mateus, Planagumà, Jesús, Martínez Hernández, Eugenia, Armangué, Thaís, Saiz Hinarejos, Albert, Gasull Casanova, Xavier, Soto del Cerro, David, Graus Ribas, Francesc, Sabater, Lidia, Dalmau Obrador, Josep, GluK2 encephalitis study group

المصدر: Articles publicats en revistes (Biomedicina)

مصطلحات موضوعية: Encefalitis, Autoimmunitat, Encephalitis, Autoimmunity

الوصف: Objective: To report the identification of antibodies against the glutamate kainate receptor subunit 2 (GluK2) in patients with autoimmune encephalitis, and describe the clinical features, IgG subclass, subunit targets, and antibody pathogenicity. Methods: Sera and CSF from 2 patients with similar brain immunostaining were used to precipitate the antigen from cultures of rat cerebellar neurons. A cell-based assay (CBA) with GluK2-expressing HEK293 cells was used to test 127 patients with unclassified neuropil antibodies, 477 with different neurological disorders, and 23 normal subjects. The IgG subclass was characterized by CBA. The effects of antibodies were determined by confocal microscopy in cultured neurons, and by electrophysiology in GluK2-expressing HEK293 cells. Results: Patients' antibodies precipitated GluK2. CBA identified 8 patients with GluK2-only antibodies, all IgG1. Six presented with acute encephalitis and clinical or MRI features of predominant cerebellar involvement and 2 developed other syndromes (1 with cerebellar involvement). Overall, 4/8 patients developed cerebellitis (2 with severe edema, compression of the 4th ventricle, and hydrocephalus). In 6 additional patients, GluK2 antibodies coexisted with AMPA (5) or NMDAR (1) antibodies and the syndrome was driven by the concurrent antibodies. GluK2 antibodies internalized GluK2 receptors in rat hippocampal neurons, and these effects were reversible. A significant reduction of GluK2-mediated currents was observed in cells treated with patients' serum following the time frame of antibody-mediated GluK2 internatization. Interpretation: GluK2 antibodies associate with an encephalitis with prominent clinical and radiological cerebellar involvement. The antibody-mediated structural and electrophysiological effects are predominantly caused by internalization of Gluk2-containing kainate receptors.

وصف الملف: 38 p.; application/pdf

العلاقة: Versió postprint del document publicat a: https://doi.org/10.1002/ana.26098Test; Annals of Neurology, 2021, vol. 90, num. 1, p. 101-117; https://doi.org/10.1002/ana.26098Test; http://hdl.handle.net/2445/183699Test; 716961; 9233317

الإتاحة: https://doi.org/10.1002/ana.26098Test
http://hdl.handle.net/2445/183699Test

المؤلفون: Comabella, Manuel, Sastre Garriga, Jaume, Borràs, Eva, Villar, Luisa M., Saiz Hinarejos, Albert, Martínez Yélamos, Sergio, García Merino, Juan Antonio, Pinteac, Rucsanda, Fissolo, Nicolás, Sánchez López, Antonio J., Costa Frossard, Lucienne, Blanco, Yolanda, Llufriu Duran, Sara, Vidal Jordana, Ángela, Sabidó Aguadé, Eduard, Montalbán Gairín, Xavier

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

مصطلحات موضوعية: Esclerosi múltiple, Marcadors bioquímics, Estudi de casos, Multiple sclerosis, Biochemical markers, Case studies

الوصف: Objective: This study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS). Methods: CSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical trial with interferon beta. Patients were classified into high and low disability progression phenotypes according to numeric progression rates (NPR) and step-based progression rates (SPR) after a mean follow-up time of 12 years. Protein abundance was measured by shotgun proteomics. Selected proteins from the discovery cohort were quantified by parallel reaction monitoring in CSF samples from an independent validation cohort of 41 patients with progressive MS classified also into high and low disability progression phenotypes after a mean follow-up time of 7 years. Results: Of 2,548 CSF proteins identified in the discovery cohort, 10 were selected for validation based on their association with long-term disability progression: SPATS2-like protein, chitinase 3-like 2 (CHI3L2), plasma serine protease inhibitor, metallothionein-3, phospholipase D4, beta-hexosaminidase, neurexophilin-1, adipocyte enhancer-binding protein 1, cathepsin L1, and lipopolysaccharide-binding protein. Only CHI3L2 was validated, and patients with high disability progression exhibited significantly higher CSF protein levels compared with patients with low disability progression (p = 0.03 for NPR and p = 0.02 for SPR). CHI3L2 levels showed good performance to discriminate between high and low disability progression in patients with progressive MS (area under the curve 0.73; sensitivity 90% and specificity 63%). Conclusions: Although further confirmatory studies are needed, we propose CSF CHI3L2 as a prognostic protein biomarker associated with long-term disability progression in patients with progressive MS.

وصف الملف: application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.1212/NXI.0000000000001082Test; Neurology - Neuroimmunology Neuroinflammation, 2021, vol. 8, num. 6, p. e1082; https://doi.org/10.1212/NXI.0000000000001082Test; http://hdl.handle.net/2445/181334Test

الإتاحة: https://doi.org/10.1212/NXI.0000000000001082Test
http://hdl.handle.net/2445/181334Test

المؤلفون: Hauser S. L., Bar-Or A., Cohen J. A., Comi G., Correale J., Coyle P. K., Cross A. H., de Seze J., Leppert D., Montalban X., Selmaj K., Wiendl H., Kerloeguen C., Willi R., Li B., Kakarieka A., Tomic D., Goodyear A., Pingili R., Haring D. A., Ramanathan K., Merschhemke M., Kappos L. Principal Investigators Argentina: Carlos Ballario, Christian Calvo Vildoso, Jorge Correale, Jorge Gustavo Jose, Norma Haydee Deri, Susana Liwacki, Australia: Jeannette Lechner-Scott, John Parratt, Suzanne Hodgkinson, Austria: Eva-Maria Maida, Fritz Leutmezer, Belgium: Barbara Willekens, Bart Van Wijmeersch, Guy Laureys, Jo Caekebeke, Karine Geens, Ludo Vanopdenbosch, Olivier Deryck, Valerie Delvaux, Vincent Van Pesch, Bulgaria: Ivan Milanov, Ivaylo Tarnev, Lyubomir Haralanov, Maria Manova Slavova, Penko Shotekov, Canada: Francois Emond, Francois Grandmaison, Francois Jacques, Liesly Lee, Marie Sarah Gagne Brosseau, Mark Freedman, Martin Cloutier, Robert Carruthers, Sarah Morrow, Yves Lapierre, Croatia: Anton Vladic, Hana Bokun, Igor Antoncic, Marija Bosnjak Pasic, Mario Habek, Silva Butkovic Soldo, Vladimira Vuletic, Czech Republic: Alena Martinkova, Eva Meluzinova, Ivana Stetkarova, Jan Mares, Jolana Markova, Marta Vachova, Martin Valis, Michaela Tyblova, Michal Dufek, Ondrej Skoda, Pavel Hradilek, Denmark: Ana 5 Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina Svendsen, Mads Ravnborg, Peter Vestergaard Rasmussen, Estonia: Katrin Gross-Paju, Sulev Haldre, Finland: Juha Pekka Eralinna, Marja-Liisa Sumelahti, France: Bruno Brochet, Celine Louapre, Christine LebrunFrenay, David Axel Laplaud, Gilles Edan, Giovanni Castelnovo, Jerome de Seze, Marc Debouverie, Patrick Vermersch, Pierre Clavelou, Pierre Labauge, Germany: Achim Berthele, Aiden Haghikia, Anselm Kornhuber, Arnfin Bergmann, Benedikt Frank, Birte EliasHamp, Bjoern Tackenberg, Brigitte Wildemann, Erik Strauss, Eugen Schlegel, Florian Then Bergh, Gereon Nelles, Hayrettin Tumani, Karl-Otto Sigel, Martin Stangel, Matthias Boehringer, Olaf Martin Hoffmann, Patrick Oschmann, Reinhard Hohlfeld, Silke Walter, Sylvia Menck, Till Sprenger, Tjalf Ziemssen, Veit Ulrich Becker, Vera Straeten, Greece: Konstantinos Kilidireas, Konstantinos Voumvourakis, Nikolaos Fakas, Nikolaos Grigoriadis, Hungary: Agnes Koves, Csilla Rozsa, Krisztina Kovacs, Laszlo Vecsei, Satori Maria, Zita Biro, India: Anshu Rohatgi, Dheeraj Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha Pandit, Meena Angamuthu Kanikannan, Pahari Ghosh, Rahul Chakor, Rahul Kulkarni, Roopkumar Gursahani, Sangeeta Ravat, Srinivasa Rangasetty, Suresh Kumar, Israel: Alla Shifrin, Arnon Karni, Radi Shahien, Ron Milo, Italy: Antonio Uccelli, Carlo Pozzilli, Francesco Sacca, Giacomo Lus, Giancarlo Comi, Girolama Alessandra Marfia, Laura Brambilla, Marco Salvetti, Massimo Filippi, Mauro Zaffaroni, Paolo Gallo, Silvia Rossi, Simona Bonavita, Valeria Studer, Latvia: Andrejs Millers, Guntis Karelis, Jolanta Kalnina, Lithuania: Dalia Mickeviciene, Rasa Kizlaitiene, Mexico: Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Netherlands: Beatrijs Wokke, Bob W Van Oosten, Peter Van Domburg, Raymond Hupperts, Rogier Q Hintzen, Norway: Astrid Edland, Peru: Cesar Castaneda, Julio Perez, Martin Gavidia, Poland: Andrzej Wiak, Bartosz Karaszewski, Elzbieta Jasinska, Halina Bartosik Psujek, Iwona Jastrzebska, Jaroslaw Slawek, Krzysztof Selmaj, Maciej Maciejowski, Miroslaw Dziki, Monika Adamczyk Sowa, Robert Bonek, Waldemar Fryze, Portugal: Ana Martins Da Silva, Angela Timoteo, Antonio Vasco Salgado, Carlos Capela, Carlos Veira, Filipe Correia, Joao Cerqueira, Joao De Sa, Livia De Sousa, Raquel Gouveia, Russia: Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, 6 Dmitry Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Slovakia: Egon Kurca, Georgi Krastev, Miroslav Brozman, Peter Koleda, Peter Turcani, Peter Valkovic, Viera Hancinova, Vladimir Donath, South Africa: Chris Retief, Michael Isaacs, Spain: Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virginia Meca Lallana, Xavier Montalban Gairin, Sweden: Fredrik Piehl, Jan Lycke, Switzerland: Chiara Zecca, Tobias Derfuss, Taiwan: Thy-sheng Lin, Thailand: Somsak Tiamkao, Turkey: Ayse Nur Yuceyar, Aysun Soysal, Belgin Petek Balci, Cavit Boz, Husnu Efendi, Murat Terzi, Serhan Sevim, Serkan Ozakbas, United Kingdom: Andrew Gale, Ben Turner, David Barnes, David Paling, Eli Silber, James Overell, Matthew Craner, USA: Aaron Carlson, Adam Wolff, Adaeze Onuoha, Adnan Subei, Ahmad Ata, Aimee Borazanci, Akram Dastagir, Alberto Vasquez, Alison Brooke Allen, Andrew P Keegan, Angel Carrasco, Angel R Chinea Martinez, Ann Bass, Annette Okai, April Erwin, Ariel Antezana-Antezana, Barbara Green, Bharathy E Sundaram, Bhupendra Khatri, Bhupesh Dihenia, Bogdan Gheorghiu, Brian Costell, Brian Steingo, Bruce L Hughes, Carrie M Hersh, Christopher Laganke, Christopher Luzzio, Corey Ford, Craig Edward Herrman, Craig Senzon, Cynthia Huffman, Daniel R Wynn, David DO Bear, David Lesch, David H Mattson, David Weisman, Deborah A Burke, Dennis W Dietrich, Deren Huang, Derrick Robertson, Djamchid Lotfi, Don Joseph Alfonso, Dusan Stefoski, Edward J Fox, Emily Pharr, Enrique Alvarez, Evanthia Bernitsas, Faria Amjad, Gabriel Pardo, Geoffrey Eubank, Gerald Mcintosh, Giles F Crowell, Hemanth Rao, J. Michael Hemphill, Jack H Florin, Jacqueline Nicholas, James Napier, James Scott, Jason M 7 Silversteen, Javier Vasallo, Jean-Raphael Schneider, Jeanette Wendt, Jeffrey Cohen, Jeffrey Gross, Jeffrey Groves, Jeffrey Kaplan, Jessica Stulc, Joanna A Cooper, John Foley, John Scagnelli, Jonathan C Calkwood, Jose Pizarro Otero, Jose Rafecas, Joshua Katz, Juliette S Saad, Katherine Standley, Keith Edwards, Kenneth Sharlin, Khurram Bashir, Kimberly Wagner, Kore Liow, Larry Lee Blankenship Jr, Laszlo Mate, Liliana Montoya, Lon D Lynn, Mark Agius, Mark Cascione, Mark Allan Goldstein, Mark Janicki, Martin R Bialow, Mary Denise Hughes, Matthew J Baker, Michelle Apperson, Michelle B Kuczma, M Mateo Paz Soldan, Mirela Cerghet, Nathaniel Robb Whaley, Paul K Winner, Pavle Repovic, Praful Kelkar, Romero, Rekha Pillai, Ricardo Ayala, Richard Sater, Randall Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert Naismith, Ronald S Murray, Samuel Hunter, Sara Qureshi, Sharon Lynch, Sibyl Wray, Silvia R Delgado, Stacy Donlon, Stanley Cohan, Stanya Smith, Stuart James Shafer, Susan Azalone, Susan Hibbs, Tamara A Miller, Thomas Giancarlo, Troy Desai, Varun K Saxena, Virginia Simnad, William David Honeycutt, William Logan, William E McElveen, William Wagner.

المساهمون: S. L., Hauser, A., Bar-Or, J. A., Cohen, G., Comi, J., Correale, P. K., Coyle, A. H., Cro, J., de Seze, D., Leppert, X., Montalban, K., Selmaj, H., Wiendl, C., Kerloeguen, R., Willi, B., Li, A., Kakarieka, D., Tomic, A., Goodyear, R., Pingili, D. A., Haring, K., Ramanathan, M., Merschhemke, Principal Investigators Argentina: Carlos Ballario, Kappos L., Calvo Vildoso, Christian, Correale, Jorge, Gustavo Jose, Jorge, Haydee Deri, Norma, Liwacki, Susana, Jeannette Lechner-Scott, Australia, Parratt, John, Hodgkinson, Suzanne, Fritz Leutmezer, Austria: Eva-Maria Maida, Barbara Willekens, Belgium, Van Wijmeersch, Bart, Laureys, Guy, Caekebeke, Jo, Geens, Karine, Vanopdenbosch, Ludo, Deryck, Olivier, Delvaux, Valerie, Van Pesch, Vincent, Ivan Milanov, Bulgaria, Tarnev, Ivaylo, Haralanov, Lyubomir, Manova Slavova, Maria, Shotekov, Penko, Francois Emond, Canada, Grandmaison, Francoi, Jacques, Francoi, Lee, Liesly, Sarah Gagne Brosseau, Marie, Freedman, Mark, Cloutier, Martin, Carruthers, Robert, Morrow, Sarah, Lapierre, Yve, Anton Vladic, Croatia, Bokun, Hana, Antoncic, Igor, Bosnjak Pasic, Marija, Habek, Mario, Butkovic Soldo, Silva, Vuletic, Vladimira, Republic: Alena Martinkova, Czech, Meluzinova, Eva, Stetkarova, Ivana, Mares, Jan, Markova, Jolana, Vachova, Marta, Valis, Martin, Tyblova, Michaela, Dufek, Michal, Skoda, Ondrej, Hradilek, Pavel, 5 Voldsgaard Jensen, Denmark: Ana, Hvilsted Nielsen, Helle, Svendsen, Kristina, Ravnborg, Mad, Vestergaard Rasmussen, Peter, Sulev Haldre, Estonia: Katrin Gross-Paju, Marja-Liisa Sumelahti, Finland: Juha Pekka Eralinna, Bruno Brochet, France, Louapre, Celine, Lebrunfrenay, Christine, Axel Laplaud, David, Edan, Gille, Castelnovo, Giovanni, de Seze, Jerome, Debouverie, Marc, Vermersch, Patrick, Clavelou, Pierre, Labauge, Pierre, Achim Berthele, Germany, Haghikia, Aiden, Kornhuber, Anselm, Bergmann, Arnfin, Frank, Benedikt, Eliashamp, Birte, Tackenberg, Bjoern, Wildemann, Brigitte

مصطلحات موضوعية: Adult, Antibodies, Monoclonal, Humanized, B-Lymphocyte, Brain, Crotonate, Disease Progression, Double-Blind Method, Female, Human, Injections, Subcutaneou, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Multiple Sclerosis, Relapsing-Remitting, T-Lymphocyte, Toluidines

الوصف: BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32757523; info:eu-repo/semantics/altIdentifier/wos/WOS:000560438400017; volume:383; issue:6; firstpage:546; lastpage:557; numberofpages:12; journal:NEW ENGLAND JOURNAL OF MEDICINE; http://hdl.handle.net/11573/1473907Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85089171143

الإتاحة: https://doi.org/10.1056/NEJMoa1917246Test
http://hdl.handle.net/11573/1473907Test