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1. MultiSCRIPT-Cycle 1—a pragmatic trial embedded within the Swiss Multiple Sclerosis Cohort (SMSC) on neurofilament light chain monitoring to inform personalized treatment decisions in multiple sclerosis: a study protocol for a randomized clinical trial

Author

Janiaud, Perrine, Zecca, Chiara, Salmen, Anke, Benkert, Pascal, Schädelin, Sabine, Orleth, Annette, Demuth, Lilian, Maceski, Aleksandra Maleska, Granziera, Cristina, Oechtering, Johanna, Leppert, David, Derfuss, Tobias, Achtnichts, Lutz, Findling, Oliver, Roth, Patrick, Lalive, Patrice, Uginet, Marjolaine, Müller, Stefanie, Pot, Caroline, Hoepner, Robert, Disanto, Giulio, Gobbi, Claudio, Rooshenas, Leila, Schwenkglenks, Matthias, Lambiris, Mark J., Kappos, Ludwig, Kuhle, Jens, Yaldizli, Özgür, and Hemkens, Lars G.

Published
2024
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5. Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study.

Author

Dekeyser, Cathérine, Hautekeete, Matthias, Cambron, Melissa, Pesch, Vincent Van, Patti, Francesco, Kuhle, Jens, Khoury, Samia, Scott, Jeanette Lechner, Gerlach, Oliver, Lugaresi, Alessandra, Maimone, Davide, Surcinelli, Andrea, Grammond, Pierre, Kalincik, Tomas, Habek, Mario, Willekens, Barbara, Macdonell, Richard, Lalive, Patrice, Csepany, Tunde, and Butzkueven, Helmut

Subjects
CEREBROSPINAL fluid, CEREBROSPINAL fluid examination, MEDICAL sciences, IMMUNOGLOBULIN light chains, PROGNOSIS
Published
2024
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6. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study

Author

Aeschbacher, Stefanie, Barakovic, Muhamed, Buser, Andreas, Chan, Andrew, Disanto, Giulio, D'Souza, Marcus, Du Pasquier, Renaud, Findling, Oliver, Galbusera, Riccardo, Hrusovsky, Kevin, Khalil, Michael, Lorscheider, Johannes, Mathias, Amandine, Orleth, Annette, Radue, Ernst-Wilhelm, Rahmanzadeh, Reza, Sinnecker, Tim, Subramaniam, Suvitha, Vehoff, Jochen, Wellmann, Sven, Wuerfel, Jens, Zecca, Chiara, Benkert, Pascal, Meier, Stephanie, Schaedelin, Sabine, Manouchehrinia, Ali, Yaldizli, Özgür, Maceski, Aleksandra, Oechtering, Johanna, Achtnichts, Lutz, Conen, David, Derfuss, Tobias, Lalive, Patrice H, Mueller, Christian, Müller, Stefanie, Naegelin, Yvonne, Oksenberg, Jorge R, Pot, Caroline, Salmen, Anke, Willemse, Eline, Kockum, Ingrid, Blennow, Kaj, Zetterberg, Henrik, Gobbi, Claudio, Kappos, Ludwig, Wiendl, Heinz, Berger, Klaus, Sormani, Maria Pia, Granziera, Cristina, Piehl, Fredrik, Leppert, David, and Kuhle, Jens

Published
2022
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9. Impact of inflammatory response in the acute phase of COVID-19 on predicting objective and subjective post-COVID fatigue

Author

Péron, Julie, primary, Nuber-Champier, Anthony, additional, Breville, Gautier, additional, Voruz, Philippe, additional, de Alcântara, Isabele Jacot, additional, Lalive, Patrice, additional, Allali, Gilles, additional, Benzakour, Lamyae, additional, Braillard, Olivia, additional, Nehme, Mayssam, additional, Coen, Matteo, additional, Serratrice, Jacques, additional, Reny, Jean-Luc, additional, Pugin, Jérôme, additional, Guessous, Idris, additional, Landis, Basile, additional, Assal, Frédéric, additional, and Peron, Julie, additional

Published
2024
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13. Persistence and emergence of new neuropsychological deficits following SARS-CoV-2 infection: A follow-up assessment of the Geneva COVID-COG cohort

Author

Voruz, Philippe, primary, de Alcântara, Isabele Jacot, additional, Nuber-Champier, Anthony, additional, Cionca, Alexandre, additional, Guérin, Delphine, additional, Allali, Gilles, additional, Benzakour, Lamyae, additional, Lalive, Patrice H, additional, Lövblad, Karl-Olof, additional, Braillard, Olivia, additional, Nencha, Umberto, additional, Nehme, Mayssam, additional, Coen, Matteo, additional, Serratrice, Jacques, additional, Reny, Jean-Luc, additional, Pugin, Jérôme, additional, Guessous, Idris, additional, Landis, Basile N, additional, Assal, Frédéric, additional, and Péron, Julie A, additional

Published
2024
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14. Besonderheiten der Immuntherapie der Multiplen Sklerose in der Schweiz: Update

Author

Friedli, Christoph, primary, Salmen, Anke, additional, Robert Hoepner, PD, additional, Achtnichts, Lutz, additional, Sandra Bigi, PD, additional, Derfuss, Tobias, additional, Gobbi, Claudio, additional, Kamber, Nicole, additional, Kamm, Christian, additional, Kuhle, Jens, additional, Lalive, Patrice, additional, Müller, Stefanie, additional, Athina Papadopoulou, PD, additional, Pot, Caroline, additional, Zecca, Chiara, additional, Chan, Andrew, additional, and Zusammenarbeit mit, in, additional

Published
2024
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15. Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS

Author

Cagol, Alessandro, primary, Benkert, Pascal, additional, Melie-Garcia, Lester, additional, Schaedelin, Sabine A., additional, Leber, Selina, additional, Tsagkas, Charidimos, additional, Barakovic, Muhamed, additional, Galbusera, Riccardo, additional, Lu, Po-Jui, additional, Weigel, Matthias, additional, Ruberte, Esther, additional, Radue, Ernst-Wilhelm, additional, Yaldizli, Özgür, additional, Oechtering, Johanna, additional, Lorscheider, Johannes, additional, D'Souza, Marcus, additional, Fischer-Barnicol, Bettina, additional, Müller, Stefanie, additional, Achtnichts, Lutz, additional, Vehoff, Jochen, additional, Disanto, Giulio, additional, Findling, Oliver, additional, Chan, Andrew, additional, Salmen, Anke, additional, Pot, Caroline, additional, Bridel, Claire, additional, Zecca, Chiara, additional, Derfuss, Tobias, additional, Lieb, Johanna M., additional, Remonda, Luca, additional, Wagner, Franca, additional, Vargas, Maria Isabel, additional, Du Pasquier, Renaud A., additional, Lalive, Patrice H., additional, Pravatà, Emanuele, additional, Weber, Johannes, additional, Cattin, Philippe C., additional, Absinta, Martina, additional, Gobbi, Claudio, additional, Leppert, David, additional, Kappos, Ludwig, additional, Kuhle, Jens, additional, and Granziera, Cristina, additional

Published
2024
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18. Glatiramer acetate treatment negatively regulates type I interferon signaling

Author

Molnarfi, Nicolas, Prod'homme, Thomas, Schulze-Topphoff, Ulf, Spencer, Collin M, Weber, Martin S, Patarroyo, Juan C, Lalive, Patrice H, and Zamvil, Scott S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Neurosciences, Autoimmune Disease, Multiple Sclerosis, Neurodegenerative, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system
Abstract

ObjectiveGlatiramer acetate (GA; Copaxone), a disease-modifying therapy for multiple sclerosis (MS), promotes development of anti-inflammatory (M2, type II) monocytes that can direct differentiation of regulatory T cells. We investigated the innate immune signaling pathways that participate in GA-mediated M2 monocyte polarization.MethodsMonocytes were isolated from myeloid differentiation primary response gene 88 (MyD88)-deficient, Toll-IL-1 receptor domain-containing adaptor inducing interferon (IFN)-β (TRIF)-deficient, IFN-α/β receptor subunit 1 (IFNAR1)-deficient, and wild-type (WT) mice and human peripheral blood. GA-treated monocytes were stimulated with Toll-like receptor ligands, then evaluated for activation of kinases and transcription factors involved in innate immunity, and secretion of proinflammatory cytokines. GA-treated mice were evaluated for cytokine secretion and susceptibility to experimental autoimmune encephalomyelitis.ResultsGA-mediated inhibition of proinflammatory cytokine production by monocytes occurred independently of MyD88 and nuclear factor-κB, but was blocked by TRIF deficiency. Furthermore, GA did not provide clinical benefit in TRIF-deficient mice. GA inhibited activation of p38 mitogen-activated protein kinase, an upstream regulator of activating transcription factor (ATF)-2, and c-Jun N-terminal kinase 1, which regulates IFN regulatory factor 3 (IRF3). Consequently, nuclear translocation of ATF-2 and IRF3, components of the IFN-β enhanceosome, was impaired. Consistent with these observations, GA inhibited production of IFN-β in vivo in WT mice, but did not modulate proinflammatory cytokine production by monocytes from IFNAR1-deficient mice.ConclusionOur results demonstrate that GA inhibits the type I IFN pathway in M2 polarization of monocytes independently of MyD88, providing an important mechanism connecting innate and adaptive immune modulation in GA therapy and valuable insight regarding its potential use with other MS treatments.

Published
2015

21. Multicentric evaluation of a specific intrathecal anti-Treponema pallidumIgG index as a diagnostic biomarker of neurosyphilis: results from a retro-prospective case–control study

Author

Alberto, Chloé, primary, Lambeng, Nathalie, additional, Deffert, Christine, additional, Breville, Gautier, additional, Gayet-Ageron, Angèle, additional, Lalive, Patrice, additional, Calmy, Alexandra, additional, Coste, Alix, additional, Papadimitriou-Olivgeris, Matthaios, additional, Braun, Dominique, additional, Lienhard, Reto, additional, Bosshard, Philipp Peter, additional, Fontao, Lionel, additional, and Toutous Trellu, Laurence, additional

Published
2023
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26. Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis

Author

Menge, Til, Lalive, Patrice H, von Büdingen, H -Christian, and Genain, Claude P

Abstract

Abstract Background Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS. Methods Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to 3 different MOG isoforms, and quantitative titers correlated with clinical characteristics. mAbs defined unique immunodominant epitopes distinct to each of the isoforms. Results In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2% of samples high-titer anti-MOG antibodies were identified. In contrast to anti-MOG reactivity observed in a mouse model of MS, in patients with MS these never reacted with ubiquitously exposed epitopes. Moreover, in patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r = 0.574; p = 0.025). Conclusions Thus high-titer reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS. Our study provides valuable information about requirements of anti-MOG reactivity for being regarded as a prognostic biomarker in a subtype of MS.

Published
2011

27. Repetitive pertussis toxin promotes development of regulatory T cells and prevents central nervous system autoimmune disease.

Author

Weber, Martin S, Benkhoucha, Mahdia, Lehmann-Horn, Klaus, Hertzenberg, Deetje, Sellner, Johann, Santiago-Raber, Marie-Laure, Chofflon, Michel, Hemmer, Bernhard, Zamvil, Scott S, and Lalive, Patrice H

Subjects
T-Lymphocytes, CD4-Positive T-Lymphocytes, Animals, Mice, Inbred C57BL, Mice, Central Nervous System Diseases, Autoimmune Diseases, Pertussis Toxin, Transforming Growth Factor beta, Interleukin-10, Cell Proliferation, Female, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Interleukin-2 Receptor alpha Subunit, Inbred C57BL, Regulatory, General Science & Technology
Abstract

Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS). Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration of pertussis toxin (PTx), the major virulence factor of Bordetella pertussis. Its adjuvant effect at the time of immunization with myelin antigen is attributed to an unspecific activation and facilitated migration of immune cells across the blood brain barrier into the central nervous system (CNS). In order to evaluate whether recurring exposure to bacterial antigen may have a differential effect on development of CNS autoimmunity, we repetitively administered PTx prior to immunization. Mice weekly injected with PTx were largely protected from subsequent EAE induction which was reflected by a decreased proliferation and pro-inflammatory differentiation of myelin-reactive T cells. Splenocytes isolated from EAE-resistant mice predominantly produced IL-10 upon re-stimulation with PTx, while non-specific immune responses were unchanged. Longitudinal analyses revealed that repetitive exposure of mice to PTx gradually elevated serum levels for TGF-β and IL-10 which was associated with an expansion of peripheral CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg). Increased frequency of Treg persisted upon immunization and thereafter. Collectively, these data suggest a scenario in which repetitive PTx treatment protects mice from development of CNS autoimmune disease through upregulation of regulatory cytokines and expansion of CD4(+)CD25(+)FoxP3(+) Treg. Besides its therapeutic implication, this finding suggests that encounter of the immune system with microbial products may not only be part of CNS autoimmune disease pathogenesis but also of its regulation.

Published
2010

28. MHC class II–restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell–mediated autoimmunity

Author

Irla, Magali, Küpfer, Natalia, Suter, Tobias, Lissilaa, Rami, Benkhoucha, Mahdia, Skupsky, Jonathan, Lalive, Patrice H, Fontana, Adriano, Reith, Walter, and Hugues, Stéphanie

Subjects
Biomedical and Clinical Sciences, Immunology, Multiple Sclerosis, Neurosciences, Neurodegenerative, Immunization, Autoimmune Disease, Brain Disorders, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Inflammatory and immune system, Animals, Antigen Presentation, Autoimmunity, B-Lymphocytes, Cell Differentiation, Cell Proliferation, Cells, Cultured, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, Histocompatibility Antigens Class II, Mice, Mice, Inbred C57BL, T-Lymphocytes, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Although plasmacytoid dendritic cells (pDCs) express major histocompatibility complex class II (MHCII) molecules, and can capture, process, and present antigens (Ags), direct demonstrations that they function as professional Ag-presenting cells (APCs) in vivo during ongoing immune responses remain lacking. We demonstrate that mice exhibiting a selective abrogation of MHCII expression by pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a consequence of enhanced priming of encephalitogenic CD4(+) T cell responses in secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph nodes and establish MHCII-dependent myelin-Ag-specific contacts with CD4(+) T cells. These interactions promote the selective expansion of myelin-Ag-specific natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4(+) T cells in vivo.

Published
2010

30. Complement Activation Is Associated With Disease Severity in Multiple Sclerosis.

Author

Oechtering, Johanna, Stein, Kerstin, Schaedelin, Sabine A., Maceski, Aleksandra M., Orleth, Annette, Meier, Stephanie, Willemse, Eline, Qureshi, Ferhan, Heijnen, Ingmar, Regeniter, Axel, Derfuss, Tobias, Benkert, Pascal, D'Souza, Marcus, Limberg, Marguerite, Fischer-Barnicol, Bettina, Achtnichts, Lutz, Mueller, Stefanie, Salmen, Anke, Lalive, Patrice H., and Bridel, Claire

Published
2024
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31. Multicentric evaluation of a specific intrathecal anti-Treponema pallidum IgG index as a diagnostic biomarker of neurosyphilis: results from a retro-prospective case-control study.

Author

Alberto, Chloé, Lambeng, Nathalie, Deffert, Christine, Breville, Gautier, Gayet-Ageron, Angèle, Lalive, Patrice, Calmy, Alexandra, Coste, Alix, Papadimitriou-Olivgeris, Matthaios, Braun, Dominique, Lienhard, Reto, Bosshard, Philipp Peter, Fontao, Lionel, and Trellu, Laurence Toutous

Published
2024
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36. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Sharmin, Sifat, primary, Roos, Izanne, additional, Simpson-Yap, Steve, additional, Malpas, Charles, additional, Sánchez, Marina M, additional, Ozakbas, Serkan, additional, Horakova, Dana, additional, Havrdova, Eva K, additional, Patti, Francesco, additional, Alroughani, Raed, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Boz, Cavit, additional, Zakaria, Magd, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Weinstock-Guttman, Bianca, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Terzi, Murat, additional, Amato, Maria Pia, additional, Karabudak, Rana, additional, Grand’Maison, Francois, additional, Khoury, Samia J, additional, Grammond, Pierre, additional, Lechner-Scott, Jeannette, additional, Buzzard, Katherine, additional, Skibina, Olga, additional, van der Walt, Anneke, additional, Butzkueven, Helmut, additional, Turkoglu, Recai, additional, Altintas, Ayse, additional, Maimone, Davide, additional, Kermode, Allan, additional, Shalaby, Nevin, additional, Pesch, Vincent V, additional, Butler, Ernest, additional, Sidhom, Youssef, additional, Gouider, Riadh, additional, Mrabet, Saloua, additional, Gerlach, Oliver, additional, Soysal, Aysun, additional, Barnett, Michael, additional, Kuhle, Jens, additional, Hughes, Stella, additional, Sa, Maria J, additional, Hodgkinson, Suzanne, additional, Oreja-Guevara, Celia, additional, Ampapa, Radek, additional, Petersen, Thor, additional, Ramo-Tello, Cristina, additional, Spitaleri, Daniele, additional, McCombe, Pamela, additional, Taylor, Bruce, additional, Prevost, Julie, additional, Foschi, Matteo, additional, Slee, Mark, additional, McGuigan, Chris, additional, Laureys, Guy, additional, Hijfte, Liesbeth V, additional, de Gans, Koen, additional, Solaro, Claudio, additional, Oh, Jiwon, additional, Macdonell, Richard, additional, Aguera-Morales, Eduardo, additional, Singhal, Bhim, additional, Gray, Orla, additional, Garber, Justin, additional, Wijmeersch, Bart V, additional, Simu, Mihaela, additional, Castillo-Triviño, Tamara, additional, Sanchez-Menoyo, Jose L, additional, Khurana, Dheeraj, additional, Al-Asmi, Abdullah, additional, Al-Harbi, Talal, additional, Deri, Norma, additional, Fragoso, Yara, additional, Lalive, Patrice H, additional, Sinnige, L G F, additional, Shaw, Cameron, additional, Shuey, Neil, additional, Csepany, Tunde, additional, Sempere, Angel P, additional, Moore, Fraser, additional, Decoo, Danny, additional, Willekens, Barbara, additional, Gobbi, Claudio, additional, Massey, Jennifer, additional, Hardy, Todd, additional, Parratt, John, additional, and Kalincik, Tomas, additional

Published
2023
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38. Obstructive sleep apnea: a major risk factor for COVID-19 encephalopathy?

Author

Breville, Gautier, primary, Herrmann, François, additional, Adler, Dan, additional, Deffert, Christine, additional, Bommarito, Giulia, additional, Stancu, Patrick, additional, Accorroni, Alice, additional, Uginet, Marjolaine, additional, Assal, Frederic, additional, Tamisier, Renaud, additional, Lalive, Patrice H., additional, Pepin, Jean-Louis, additional, Lövblad, Karl-Olof, additional, and Allali, Gilles, additional

Published
2023
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39. Serum Glial Fibrillary Acidic Protein compared with Neurofilament Light Chain as Biomarker for Multiple Sclerosis Disease Progression (P5-3.016)

Author

Meier, Stephanie, primary, Benkert, Pascal, additional, Maceski, Aleksandra Maleska, additional, Schaedelin, Sabine, additional, Oechtering, Johanna, additional, Melie-Garcia, Lester, additional, Cagol, Alessandro, additional, Barakovic, Muhamed, additional, Galbusera, Riccardo, additional, Achtnichts, Lutz, additional, Lalive, Patrice H., additional, Bridel, Claire, additional, Müller, Stefanie, additional, Pot, Caroline, additional, Salmen, Anke, additional, Disanto, Giulio, additional, Zecca, Chiara, additional, Abdelhak, Ahmed, additional, Barro, Christian, additional, Thebault, Simon, additional, D’Souza, Marcus, additional, Derfuss, Tobias, additional, Orleth, Annette, additional, Khalil, Michael, additional, Yaldizli, Özguer, additional, Hermesdorf, Marco, additional, Wiendl, Heinz, additional, Piehl, Fredrik, additional, Fischer, Urs, additional, Kappos, Ludwig, additional, Gobbi, Claudio, additional, Granziera, Cristina, additional, Leppert, David, additional, Willemse, Eline A.J., additional, and Kuhle, Jens, additional

Published
2023
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40. Multicentric evaluation of a specific intrathecal anti-Treponema pallidumIgG index as a diagnostic biomarker of neurosyphilis: results from a retro-prospective case–control study

Author

Alberto, Chloé, Lambeng, Nathalie, Deffert, Christine, Breville, Gautier, Gayet-Ageron, Angèle, Lalive, Patrice, Calmy, Alexandra, Coste, Alix, Papadimitriou-Olivgeris, Matthaios, Braun, Dominique, Lienhard, Reto, Bosshard, Philipp Peter, Fontao, Lionel, and Toutous Trellu, Laurence

Abstract

Background and objectivesThe diagnosis of neurosyphilis (NS) lacks a true ‘gold standard’, making the diagnosis challenging while consequences of a misdiagnosis are potentially severe. The aim of this study was to evaluate the diagnostic performance of measuring an antibody index (AI) for the intrathecal synthesis of specific anti-Treponema pallidum(T. pallidum) IgG for the diagnosis of NS.MethodsSpecific anti-T. pallidumIgG were measured simultaneously in paired cerebrospinal fluid (CSF)–serum samples collected retrospectively and prospectively between 2007 and 2022, from patients suspected of NS, in Switzerland. An AI was calculated to account for blood–brain barrier integrity. Area under the receiver operating characteristic curve, sensitivity/specificity and positive/negative predictive values of AI test were estimated. Two NS definitions were used: NS1 included patients with NS suspicion presenting with neurological symptoms and/or acute neurosensory signs, and positive T. PallidumHemagglutinations Assay (TPHA)/T. pallidumparticle agglutination assay (TPPA) serology and CSF-TPHA/TPPA ≥320, and either CSF-leucocytes >5 cells/mm3and/or CSF-protein >0.45 g/L and/or a reactive CSF-venereal disease research laboratory (VDRL)/rapid plasma reagin (RPR) test. NS2 included patients with suspected NS presenting with acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other central nervous system (CNS) pathologies and with positive TPHA/TPPA serology.ResultsThe study included 71 NS (43 NS1 and 28 NS2) and 110 controls. With a threshold of ≥1.7, sensitivity and specificity of the specific AI test were 90.7% (CI 77.7 to 97.4) and 100% (CI 96.7 to 100.0), respectively, for NS1 and 14.3% (CI 4 to 32.7) and 100% (CI 96.7 to 100.0) for NS2. In patients suspected of NS with a CNS involvement (NS1 group), NS could be confirmed by the positivity of this specific AI.ConclusionsMeasurement of an intrathecal synthesis index of specific anti-T. pallidumIgG in patients with CSF inflammatory signs appears to be a valuable diagnostic test. However, in otic or ocular syphilis, presenting few CSF abnormalities, AI is not sufficient alone to confirm NS diagnosis.Trial registrationSwiss Association of Research Ethics Committees number 2019-00232.

Published
2024
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41. Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis.

Author

Abdelhak, Ahmed, Benkert, Pascal, Schaedelin, Sabine, Boscardin, W. John, Cordano, Christian, Oechtering, Johanna, Ananth, Kirtana, Granziera, Cristina, Melie-Garcia, Lester, Montes, Shivany Condor, Beaudry-Richard, Alexandra, Achtnichts, Lutz, Oertel, Frederike C., Lalive, Patrice H., Leppert, David, Müller, Stefanie, Henry, Roland G., Pot, Caroline, Matthias, Amandine, and Salmen, Anke

Published
2023
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42. c-Met + Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models.

Author

Benkhoucha, Mahdia, Tran, Ngoc Lan, Senoner, Isis, Breville, Gautier, Fritah, Hajer, Migliorini, Denis, Dutoit, Valérie, and Lalive, Patrice H.

Subjects
CYTOTOXIC T cells, IMMUNE checkpoint proteins, HUMAN cloning, CYTOTOXINS, IPILIMUMAB, HEPATOCYTE growth factor, MICROPHTHALMIA-associated transcription factor, MELANOMA
Abstract

CD8+ cytotoxic T lymphocytes (CTLs) play a crucial role in anti-tumor immunity. In a previous study, we identified a subset of murine effector CTLs expressing the hepatocyte growth factor (HGF) receptor, c-Met (c-Met+ CTLs), that are endowed with enhanced cytolytic capacity. HGF directly inhibited the cytolytic function of c-Met+ CTLs, both in 2D in vitro assays and in vivo, leading to reduced T cell responses against metastatic melanoma. To further investigate the role of c-Met+ CTLs in a three-dimensional (3D) setting, we studied their function within B16 melanoma spheroids and examined the impact of cell–cell contact on the modulation of inhibitory checkpoint molecules' expression, such as KLRG1, PD-1, and CTLA-4. Additionally, we evaluated the cytolytic capacity of human CTL clones expressing c-Met (c-Met+) and compared it to c-Met− CTL clones. Our results indicated that, similar to their murine counterparts, c-Met+ human CTL clones exhibited increased cytolytic activity compared to c-Met− CTL clones, and this enhanced function was negatively regulated by the presence of HGF. Taken together, our findings highlight the potential of targeting the HGF/c-Met pathway to modulate CTL-mediated anti-tumor immunity. This research holds promise for developing strategies to enhance the effectiveness of CTL-based immunotherapies against cancer. [ABSTRACT FROM AUTHOR]

Published
2023
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44. Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis

Author

Meier, Stephanie, primary, Willemse, Eline A.J., additional, Schaedelin, Sabine, additional, Oechtering, Johanna, additional, Lorscheider, Johannes, additional, Melie-Garcia, Lester, additional, Cagol, Alessandro, additional, Barakovic, Muhamed, additional, Galbusera, Riccardo, additional, Subramaniam, Suvitha, additional, Barro, Christian, additional, Abdelhak, Ahmed, additional, Thebault, Simon, additional, Achtnichts, Lutz, additional, Lalive, Patrice, additional, Müller, Stefanie, additional, Pot, Caroline, additional, Salmen, Anke, additional, Disanto, Giulio, additional, Zecca, Chiara, additional, D’Souza, Marcus, additional, Orleth, Annette, additional, Khalil, Michael, additional, Buchmann, Arabella, additional, Du Pasquier, Renaud, additional, Yaldizli, Özgür, additional, Derfuss, Tobias, additional, Berger, Klaus, additional, Hermesdorf, Marco, additional, Wiendl, Heinz, additional, Piehl, Fredrik, additional, Battaglini, Marco, additional, Fischer, Urs, additional, Kappos, Ludwig, additional, Gobbi, Claudio, additional, Granziera, Cristina, additional, Bridel, Claire, additional, Leppert, David, additional, Maleska Maceski, Aleksandra, additional, Benkert, Pascal, additional, and Kuhle, Jens, additional

Published
2023
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46. Markers of limbic system damage following SARS-CoV-2 infection

Author

Thomasson, Marine, primary, Voruz, Philippe, additional, Cionca, Alexandre, additional, Jacot de Alcântara, Isabele, additional, Nuber-Champier, Anthony, additional, Allali, Gilles, additional, Benzakour, Lamyae, additional, Lalive, Patrice H, additional, Lövblad, Karl-Olof, additional, Braillard, Olivia, additional, Nehme, Mayssam, additional, Coen, Matteo, additional, Serratrice, Jacques, additional, Reny, Jean-Luc, additional, Pugin, Jérôme, additional, Guessous, Idris, additional, Landis, Basile N, additional, Griffa, Alessandra, additional, Van De Ville, Dimitri, additional, Assal, Frederic, additional, and Péron, Julie A, additional

Published
2023
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48. Comparative effectiveness of autologous hematopoietic stem cell transplant vs Fingolimod, Natalizumab, and Ocrelizumab in highly active relapsing-remitting multiple sclerosis

Author

Kalincik, Tomas, Sharmin, Sifat, Roos, Izanne, Freedman, Mark S., Atkins, Harold, Burman, Joachim, Massey, Jennifer, Sutton, Ian, Withers, Barbara, Macdonell, Richard, Grigg, Andrew, Torkildsen, Øivind, Bo, Lars, Lehmann, Anne Kristine, Havrdova, Eva Kubala, Krasulova, Eva, Trněný, Marek, Kozak, Tomas, van der Walt, Anneke, Butzkueven, Helmut, McCombe, Pamela, Skibina, Olga, Lechner-Scott, Jeannette, Willekens, Barbara, Cartechini, Elisabetta, Ozakbas, Serkan, Alroughani, Raed, Kuhle, Jens, Patti, Francesco, Duquette, Pierre, Lugaresi, Alessandra, Khoury, Samia J., Slee, Mark, Turkoglu, Recai, Hodgkinson, Suzanne, John, Nevin, Maimone, Davide, Sa, Maria Jose, van Pesch, Vincent, Gerlach, Oliver, Laureys, Guy, Van Hijfte, Liesbeth, Karabudak, Rana, Spitaleri, Daniele, Csepany, Tunde, Gouider, Riadh, Castillo-Triviño, Tamara, Taylor, Bruce, Sharrack, Basil, Snowden, John A., Horakova, Dana, Buzzard, Katherine, Terzi, Murat, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Barnett, Michael, Stewart, Grace, Onofrj, Marco, Izquierdo, Guillermo, Eichau, Sara, Grand'Maison, Francois, Prevost, Julie, Van Wijmeersch, Bart, Amato, Maria Pia, Shaygannejad, Vahid, Boz, Cavit, Bolaños, Ricardo Fernandez, Soysal, Aysun, Ramo-Tello, Cristina, Solaro, Claudio, Gobbi, Claudio, Cabrera-Gomez, Jose Antonio, Roullet, Etienne, Zwanikken, Cees, Den braber-Moerland, Leontien, Deri, Norma, Saladino, Maria Laura, Cristiano, Edgardo, Rojas, Juan Ignacio, Vrech, Carlos, Shaw, Cameron, Shuey, Neil, Boggild, Mike, Tan, Ik Lin, Hardy, Todd, Decoo, Danny, Moore, Fraser, Oh, Jiwon, Lalive, Patrice, Ampapa, Radek, Petersen, Thor, Oreja-Guevara, Celia, Perez Sempere, Angel, Dominguez, Jose Andres, Besora, Sarah, Hughes, Stella, Gray, Orla, Grigoriadis, Nikolaos, Piroska, Imre, Rozsa, Csilla, Kasa, Krisztian, Simo, Magdolna, Kovacs, Krisztina, Sas, Attila, Dobos, Eniko, Rajda, Cecilia, McGuigan, Chris, Mason, Deborah, Schepel, Jan, Alkhaboori, Jabir, Rio, Maria Edite, Mihaela, Simu, Al-Harbi, Talal, Altintas, Ayse, Kister, Ilya, Marriott, Mark, Kilpatrick, Trevor, King, John, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Taylor, Lisa, Diamanti, Matteo, Chisari, Clara, Toscano, Simona, Salvatore, Lo Fermo, Larochelle, Catherine, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Hupperts, Raymond, Olascoaga, Javier, Saiz, Albert, Zivadinov, Robert, Benedict, Ralph, Verheul, Freek, Fabis-Pedrini, Marzena, Mrabet, Saloua, Garber, Justin, Sanchez-Menoyo, Jose Luis, Aguera-Morales, Eduardo, Blanco, Yolanda, Al-Asmi, Abdullah, Weinstock-Guttman, Bianca, Fragoso, Yara, de Gans, Koen, and Kermode, Allan

Subjects
Human medicine
Abstract

you are agreeing to our Cookie Policy | Continue JAMA Network HomeJAMA Neurology This Issue Views 2,357 Citations 0 60 Full Text Share Comment Original Investigation May 15, 2023 Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis Tomas Kalincik, MD, PhD1,2; Sifat Sharmin, PhD1,2; Izanne Roos, MBChB, PhD1,2; Mark S. Freedman, MD3; Harold Atkins, MD4; Joachim Burman, MD, PhD5; Jennifer Massey, MBBS, PhD6,7; Ian Sutton, MBBS, PhD6,8; Barbara Withers, MD, PhD7,9; Richard Macdonell, MD, PhD10,11; Andrew Grigg, MD, PhD11,12; Øivind Torkildsen, MD, PhD13; Lars Bo, MD, PhD13; Anne Kristine Lehmann, MD, PhD14; Eva Kubala Havrdova, MD, PhD15; Eva Krasulova, MD, PhD15; Marek Trněný, MD, PhD16; Tomas Kozak, MD, PhD17; Anneke van der Walt, MBBS, PhD18,19; Helmut Butzkueven, MBBS, PhD18,19; Pamela McCombe, MBBS20,21; Olga Skibina, MBBS18,22,23; Jeannette Lechner-Scott, MD, PhD24,25; Barbara Willekens, MD, PhD26,27; Elisabetta Cartechini, MD28; Serkan Ozakbas, MD29; Raed Alroughani, MD30; Jens Kuhle, MD, PhD31; Francesco Patti, MD32,33; Pierre Duquette, MD34; Alessandra Lugaresi, MD, PhD35,36; Samia J. Khoury, MD, PhD37; Mark Slee, MD, PhD38; Recai Turkoglu, MD39; Suzanne Hodgkinson, MD40; Nevin John, MD, PhD41,42; Davide Maimone, MD43; Maria Jose Sa, MD44; Vincent van Pesch, MD, PhD45,46; Oliver Gerlach, MD, PhD47,48; Guy Laureys, MD49; Liesbeth Van Hijfte, MD49; Rana Karabudak, MD50; Daniele Spitaleri, MD51; Tunde Csepany, MD, PhD52; Riadh Gouider, MD53,54; Tamara Castillo-Triviño, MD55; Bruce Taylor, MD, PhD56,57; Basil Sharrack, MD, PhD58; John A. Snowden, MD, PhD59; and the MSBase Study Group Collaborators; and the MSBase Study Group Authors Author Affiliations JAMA Neurol. 2023;80(7):702-713. doi:10.1001/jamaneurol.2023.1184 editorial comment iconEditorial Comment Key Points Question What is the comparative effectiveness of autologous hematopoietic stem cell transplant (AHSCT) vs individual most potent disease-modifying therapies for relapsing-remitting multiple sclerosis (MS), such as natalizumab or ocrelizumab? Findings In this observational comparative effectiveness study of 4915 individuals using a composite cohort from specialized MS centers and the MSBase international registry, the effectiveness of AHSCT was compared with 1 medium-efficacy and 2 high-efficacy disease-modifying therapies (fingolimod, natalizumab, and ocrelizumab) in patients with relapsing-remitting MS, high frequency of relapses, and moderate disability. Over 5 years, AHSCT was associated with substantially lower relapse rate than fingolimod and marginally lower relapse rate than natalizumab and was also associated with a higher rate of recovery from disability compared with fingolimod and natalizumab, but no evidence of difference in clinical outcomes between AHSCT and ocrelizumab was found at 3-year follow-up. Meaning The results indicate that in relapsing-remitting MS, the clinical effectiveness of AHSCT is considerably superior to fingolimod and marginally superior to natalizumab. Abstract Importance Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.

Published
2023

49. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Sharmin, Sifat, Roos, Izanne, Simpson-Yap, Steve, Malpas, Charles, Sánchez, Marina M, Ozakbas, Serkan, Horakova, Dana, Havrdova, Eva K, Patti, Francesco, Alroughani, Raed, Izquierdo, Guillermo, Eichau, Sara, Boz, Cavit, Zakaria, Magd, Onofrj, Marco, Lugaresi, Alessandra, Weinstock-Guttman, Bianca, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Terzi, Murat, Amato, Maria Pia, Karabudak, Rana, Grand'Maison, Francois, Khoury, Samia J, Grammond, Pierre, Lechner-Scott, Jeannette, Buzzard, Katherine, Skibina, Olga, van der Walt, Anneke, Butzkueven, Helmut, Turkoglu, Recai, Altintas, Ayse, Maimone, Davide, Kermode, Allan, Shalaby, Nevin, Pesch, Vincent V, Butler, Ernest, Sidhom, Youssef, Gouider, Riadh, Mrabet, Saloua, Gerlach, Oliver, Soysal, Aysun, Barnett, Michael, Kuhle, Jens, Hughes, Stella, Maria J, Sa, Hodgkinson, Suzanne, Oreja-Guevara, Celia, Ampapa, Radek, Petersen, Thor, Ramo-Tello, Cristina, Spitaleri, Daniele, Mccombe, Pamela, Taylor, Bruce, Prevost, Julie, Foschi, Matteo, Slee, Mark, Mcguigan, Chris, Laureys, Guy, Hijfte, Liesbeth V, de Gans, Koen, Solaro, Claudio, Jiwon, Oh, Macdonell, Richard, Aguera-Morales, Eduardo, Singhal, Bhim, Gray, Orla, Garber, Justin, Wijmeersch, Bart V, Simu, Mihaela, Triviño, Tamara C, Sanchez-Menoyo, Jose L, Khurana, Dheeraj, Al-Asmi, Abdullah, Al-Harbi, Talal, Deri, Norma, Fragoso, Yara, Lalive, Patrice H, Sinnige, L G F, Shaw, Cameron, Shuey, Neil, Csepany, Tunde, Sempere, Angel P, Moore, Fraser, Decoo, Danny, Willekens, Barbara, Gobbi, Claudio, Massey, Jennifer, Hardy, Todd, Parratt, John, and Kalincik, Tomas

Subjects
secondary progressive multiple sclerosis, health expenditure, disease-modifying therapy, geography, latitude
Published
2023

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