125 results on '"Pignolet, Béatrice"'
Search Results
2. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
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German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network, Ostkamp, Patrick, Salmen, Anke, Pignolet, Béatrice, Görlich, Dennis, Andlauer, Till F. M., Schulte-Mecklenbeck, Andreas, Gonzalez-Escamilla, Gabriel, Bucciarelli, Florence, Gennero, Isabelle, Breuer, Johanna, Antony, Gisela, Schneider-Hohendorf, Tilman, Mykicki, Nadine, Bayas, Antonios, Bergh, Florian Then, Bittner, Stefan, Hartung, Hans-Peter, Friese, Manuel A., Linker, Ralf A., Luessi, Felix, Lehmann-Horn, Klaus, Mühlau, Mark, Paul, Friedemann, Stangel, Martin, Tackenberg, Björn, Tumani, Hayrettin, Warnke, Clemens, Weber, Frank, Wildemann, Brigitte, Zettl, Uwe K., Ziemann, Ulf, Müller-Myhsok, Bertram, Kümpfel, Tania, Klotz, Luisa, Meuth, Sven G., Zipp, Frauke, Hemmer, Bernhard, Hohlfeld, Reinhard, Brassat, David, Gold, Ralf, Gross, Catharina C., Lukas, Carsten, Groppa, Sergiu, Loser, Karin, Wiendl, Heinz, and Schwab, Nicholas
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- 2021
3. Prospective validation of the PML risk biomarker L-Selectin and influence of natalizumab extended intervals
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Schwab, Nicholas, Schneider-Hohendorf, Tilman, Pignolet, Béatrice, Bucciarelli, Florence, Scandella, Lise, Ciron, Jonathan, Biotti, Damien, Lebrun-Frenay, Christine, Mathey, Guillaume, Clavelou, Pierre, Pelletier, Jean, Ostkamp, Patrick, Meinl, Ingrid, Windhagen, Susanne, Klotz, Luisa, Gross, Catharina C., Meuth, Sven G., Deisenhammer, Florian, Brassat, David, and Wiendl, Heinz
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- 2019
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4. CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice
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Bernard-Valnet, Raphaël, Yshii, Lidia, Quériault, Clémence, Nguyen, Xuan-Hung, Arthaud, Sébastien, Rodrigues, Magda, Canivet, Astrid, Morel, Anne-Laure, Matthys, Arthur, Bauer, Jan, Pignolet, Béatrice, Dauvilliers, Yves, Peyron, Christelle, and Liblau, Roland S.
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- 2016
5. Intrinsic-Dimension Analysis for Guiding Dimensionality Reduction in Multi-Omics Data
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Guarino, Valentina, primary, Gliozzo, Jessica, additional, Clarelli, Ferdinando, additional, Pignolet, Béatrice, additional, Misra, Kaalindi, additional, Mascia, Elisabetta, additional, Antonino, Giordano, additional, Santoro, Silvia, additional, Ferré, Laura, additional, Cannizzaro, Miryam, additional, Sorosina, Melissa, additional, Liblau, Roland, additional, Filippi, Massimo, additional, Mosca, Ettore, additional, Esposito, Federica, additional, Valentini, Giorgio, additional, and Casiraghi, Elena, additional
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- 2023
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6. Correction: Broader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis
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Schneider-Hohendorf, Tilman, primary, Gerdes, Lisa Ann, additional, Pignolet, Béatrice, additional, Gittelman, Rachel, additional, Ostkamp, Patrick, additional, Rubelt, Florian, additional, Raposo, Catarina, additional, Tackenberg, Björn, additional, Riepenhausen, Marianne, additional, Janoschka, Claudia, additional, Wünsch, Christian, additional, Bucciarelli, Florence, additional, Flierl-Hecht, Andrea, additional, Beltrán, Eduardo, additional, Kümpfel, Tania, additional, Anslinger, Katja, additional, Gross, Catharina C., additional, Chapman, Heidi, additional, Kaplan, Ian, additional, Brassat, David, additional, Wekerle, Hartmut, additional, Kerschensteiner, Martin, additional, Klotz, Luisa, additional, Lünemann, Jan D., additional, Hohlfeld, Reinhard, additional, Liblau, Roland, additional, Wiendl, Heinz, additional, and Schwab, Nicholas, additional
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- 2022
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7. Broader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis
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Schneider-Hohendorf, Tilman, primary, Gerdes, Lisa Ann, additional, Pignolet, Béatrice, additional, Gittelman, Rachel, additional, Ostkamp, Patrick, additional, Rubelt, Florian, additional, Raposo, Catarina, additional, Tackenberg, Björn, additional, Riepenhausen, Marianne, additional, Janoschka, Claudia, additional, Wünsch, Christian, additional, Bucciarelli, Florence, additional, Flierl-Hecht, Andrea, additional, Beltrán, Eduardo, additional, Kümpfel, Tania, additional, Anslinger, Katja, additional, Gross, Catharina C., additional, Chapman, Heidi, additional, Kaplan, Ian, additional, Brassat, David, additional, Wekerle, Hartmut, additional, Kerschensteiner, Martin, additional, Klotz, Luisa, additional, Lünemann, Jan D., additional, Hohlfeld, Reinhard, additional, Liblau, Roland, additional, Wiendl, Heinz, additional, and Schwab, Nicholas, additional
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- 2022
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8. Reply
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Fissolo, Nicolas, Pignolet, Béatrice, Brassat, David, and Comabella, Manuel
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- 2017
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9. Genetic factors implicated in the response to fingolimod treatment in multiple sclerosis patients: results from a pharmacogenetic meta-analysis
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Ferrè, Laura, Mascia, Elisabetta, Clarelli, Ferdinando, Roostaei, Tina, Pignolet, Beatrice, Brassat, David, Liblau, Roland, Weiner, Howard, De Jager, Philip, Filippi, Massimo, and Esposito, Federica
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- 2021
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10. Transgenic mouse models of multiple sclerosis
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Scheikl, Tanja, Pignolet, Béatrice, Mars, Lennart T., and Liblau, Roland S.
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- 2010
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11. BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS
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Cohen, Mikael, Mondot, Lydiane, Bucciarelli, Florence, Pignolet, Béatrice, Laplaud, David-Axel, Wiertlewski, Sandrine, Brochet, Bruno, Ruet, Aurélie, Defer, Gilles, Derache, Nathalie, Vermersch, Patrick, Zephir, Hélène, Debouverie, Marc, Mathey, Guillaume, Berger, Eric, Cappé, Chrystelle, Labauge, Pierre, Carra, Clarisse, de Seze, Jérôme, Bigaut, Kevin, Brassat, David, Lebrun-Frenay, Christine, Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Neurologie [Strasbourg], and CHU Strasbourg-Hopital Civil
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MESH: Humans ,[SDV]Life Sciences [q-bio] ,MESH: Multiple Sclerosis ,MESH: Natalizumab / therapeutic use ,MESH: Prospective Studies ,Multiple sclerosis ,MESH: Fingolimod Hydrochloride* / therapeutic use ,natalizumab ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,therapeutics ,magnetic resonance imaging ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,fingolimod ,MESH: Neoplasm Recurrence, Local - Abstract
International audience; Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS) Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing–remitting MS Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY.
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- 2020
12. Author response: Prospective validation of the PML risk biomarker l -selectin and influence of natalizumab extended intervals
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Schwab, Nicholas, primary, Schneider-Hohendorf, Tilman, additional, Pignolet, Béatrice, additional, Brassat, David, additional, and Wiendl, Heinz, additional
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- 2020
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13. BEST MS : étude nationale prospective comparant l’efficacité du natalizumab et du fingolimod dans les formes actives de sclérose en plaques
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Cohen, Mikael, primary, Mondot, Lydiane, additional, Bucciarelli, Florence, additional, Pignolet, Béatrice, additional, Laplaud, David-Axel, additional, Brochet, Bruno, additional, Defer, Gilles, additional, Vermersch, Patrick, additional, Debouverie, Marc, additional, Berger, Eric, additional, Labauge, Pierre, additional, De Sèze, Jérôme, additional, Brassat, David, additional, and Lebrun, Christine, additional
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- 2020
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14. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
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Ostkamp, Patrick, primary, Salmen, Anke, additional, Pignolet, Béatrice, additional, Görlich, Dennis, additional, Andlauer, Till F. M., additional, Schulte-Mecklenbeck, Andreas, additional, Gonzalez-Escamilla, Gabriel, additional, Bucciarelli, Florence, additional, Gennero, Isabelle, additional, Breuer, Johanna, additional, Antony, Gisela, additional, Schneider-Hohendorf, Tilman, additional, Mykicki, Nadine, additional, Bayas, Antonios, additional, Bergh, Florian Then, additional, Bittner, Stefan, additional, Hartung, Hans-Peter, additional, Friese, Manuel A., additional, Linker, Ralf A., additional, Luessi, Felix, additional, Lehmann-Horn, Klaus, additional, Mühlau, Mark, additional, Paul, Friedemann, additional, Stangel, Martin, additional, Tackenberg, Björn, additional, Tumani, Hayrettin, additional, Warnke, Clemens, additional, Weber, Frank, additional, Wildemann, Brigitte, additional, Zettl, Uwe K., additional, Ziemann, Ulf, additional, Müller-Myhsok, Bertram, additional, Kümpfel, Tania, additional, Klotz, Luisa, additional, Meuth, Sven G., additional, Zipp, Frauke, additional, Hemmer, Bernhard, additional, Hohlfeld, Reinhard, additional, Brassat, David, additional, Gold, Ralf, additional, Gross, Catharina C., additional, Lukas, Carsten, additional, Groppa, Sergiu, additional, Loser, Karin, additional, Wiendl, Heinz, additional, and Schwab, Nicholas, additional
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- 2020
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15. BEST-MS: A Standardized and Prospective Study Comparing the Efficacy of Natalizumab versus Fingolimod in Active Relapsing Multiple Sclerosis. (769)
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Cohen, Mikael, primary, Mondot, Lydiane, additional, BUCCIARELLI, Florence, additional, PIGNOLET, Béatrice, additional, LAPLAUD, David, additional, Brochet, Bruno, additional, Defer, Gilles, additional, Derache, Nathalie, additional, Vermersch, Patrick, additional, ZEPHIR, Hélène, additional, Debouverie, Marc, additional, Berger, Eric, additional, Labauge, Pierre, additional, Ayrignac, Xavier, additional, De Seze, Jerome, additional, Brassat, David, additional, and Lebrun-Frenay, Christine, additional
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- 2020
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16. BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS.
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Cohen, Mikael, Mondot, Lydiane, Bucciarelli, Florence, Pignolet, Béatrice, Laplaud, David-Axel, Wiertlewski, Sandrine, Brochet, Bruno, Ruet, Aurélie, Defer, Gilles, Derache, Nathalie, Vermersch, Patrick, Zephir, Hélène, Debouverie, Marc, Mathey, Guillaume, Berger, Eric, Cappé, Chrystelle, Labauge, Pierre, Carra, Clarisse, De Seze, Jérôme, and Bigaut, Kevin
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NATALIZUMAB ,MAGNETIC resonance imaging ,PHYSICIANS ,FINGOLIMOD - Abstract
Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS) Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing–remitting MS Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group (p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects
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Klotz, Luisa, primary, Eschborn, Melanie, additional, Lindner, Maren, additional, Liebmann, Marie, additional, Herold, Martin, additional, Janoschka, Claudia, additional, Torres Garrido, Belén, additional, Schulte-Mecklenbeck, Andreas, additional, Gross, Catharina C., additional, Breuer, Johanna, additional, Hundehege, Petra, additional, Posevitz, Vilmos, additional, Pignolet, Béatrice, additional, Nebel, Giulia, additional, Glander, Shirin, additional, Freise, Nicole, additional, Austermann, Judith, additional, Wirth, Timo, additional, Campbell, Graham R., additional, Schneider-Hohendorf, Tilman, additional, Eveslage, Maria, additional, Brassat, David, additional, Schwab, Nicholas, additional, Loser, Karin, additional, Roth, Johannes, additional, Busch, Karin B., additional, Stoll, Monika, additional, Mahad, Don J., additional, Meuth, Sven G., additional, Turner, Timothy, additional, Bar-Or, Amit, additional, and Wiendl, Heinz, additional
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- 2019
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18. IFN-γ is a therapeutic target in paraneoplastic cerebellar degeneration
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Yshii, Lidia, primary, Pignolet, Béatrice, additional, Mauré, Emilie, additional, Pierau, Mandy, additional, Brunner-Weinzierl, Monika, additional, Hartley, Oliver, additional, Bauer, Jan, additional, and Liblau, Roland, additional
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- 2019
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19. Existe-t-il un biomarqueur universel sanguin de réponse aux traitements dans la sclérose en plaques ? Étude UBITMUS (Universal BIomarker of Treatment in MS)
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Pignolet, Béatrice, primary, Biotti, Damien, additional, De Seze, Jérôme, additional, Brochet, Bruno, additional, Debouverie, Marc, additional, Defer, Gilles, additional, Hautecoeur, Patrick, additional, Labauge, Pierre, additional, Clavelou, Pierre, additional, Pelletier, Jean, additional, Laplaud, David-Axel, additional, Vermersch, Patrick, additional, Lebrun-Frenay, Christine, additional, Thouvenot, Eric, additional, and Brassat, David, additional
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- 2019
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20. In vitro permissivity of bovine cells for wild-type and vaccinal myxoma virus strains
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Foucras Gilles, Gelfi Jacqueline, Allemandou Aude, Duteyrat Jean-Luc, Pignolet Béatrice, and Bertagnoli Stéphane
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Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Myxoma virus (MYXV), a leporide-specific poxvirus, represents an attractive candidate for the generation of safe, non-replicative vaccine vector for non-host species. However, there is very little information concerning infection of non-laboratory animals species cells with MYXV. In this study, we investigated interactions between bovine cells and respectively a wild type strain (T1) and a vaccinal strain (SG33) of MYXV. We showed that bovine KOP-R, BT and MDBK cell lines do not support MYXV production. Electron microscopy observations of BT-infected cells revealed the low efficiency of viral entry and the production of defective virions. In addition, infection of bovine peripheral blood mononuclear cells (PBMC) occurred at a very low level, even following non-specific activation, and was always abortive. We did not observe significant differences between the wild type strain and the vaccinal strain of MYXV, indicating that SG33 could be used for new bovine vaccination strategies.
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- 2007
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21. MMP9 is decreased in natalizumab-treated MS patients at risk for PML
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Fissolo, Nicolas, Pignolet, Béatrice, Matute-Blanch, Clara, Triviño, Juan Carlos, Miró, Berta, Mota, Miriam, Perez-Hoyos, Santiago, Sanchez, Alex, Vermersch, Patrick, Ruet, Aurélie, Sèze, Jérome, Labauge, Pierre, Vukusic, Sandra, Papeix, Caroline, Almoyna, Laurent, Tourbah, Ayman, Clavelou, Pierre, Moreau, Thibault, Pelletier, Jean, Lebrun-Frenay, Christine, Montalban, Xavier, Brassat, David, Comabella, Manuel, BIONAT, BEST-MS, network, SFSEP, Departamento de Fisica Aplicada [Bilbao], Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Statistics Department, University of Barcelona, Institut de Recerca, Vall d'Hebron University Hospital [Barcelona], Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Service de neurologie D, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Bordeaux (UB), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurocentre Magendie-U862, Institut François Magendie, and Université de Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), CIC de Strasbourg, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Hospices civils de Lyon - Hôpital Pierre Wertheimer], Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de compétence de la Sclérose Latérale Amyotrophique [CHU Clermont-Ferrand] (SLA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Nice (CHU Nice), Medical Image Analysis Center (MIAC AG), Neurologie vasculaire, pathologie neuro-dégénérative et explorations fonctionnelles du système nerveux [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,parasitic diseases ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,snc - Abstract
International audience; OBJECTIVE: To identify biomarkers associated with the development of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab (NTZ). METHODS: Relapsing-remitting MS (RRMS) patients who developed PML under NTZ therapy (pre-PML) and non-PML natalizumab-treated patients (NTZ-ctr) were included in the study. Cryopreserved peripheral blood mononuclear cells (PBMC) and serum samples collected at baseline, at one- and two-year treated time points, and during PML were analyzed for gene expression by RNA-sequencing and for serum protein levels by LUMINEX and ELISA assays respectively. RESULTS: Among top differentially expressed genes in the RNA-sequencing between pre-PML and NTZ-ctr patients, pathway analysis revealed a high representation of genes belonging to the following categories: pro-angiogenic factors (MMP9, VEGFA), chemokines (CXCL1, CXCL5, IL8, CCL2), cytokines (IL1B, IFNG), and plasminogen- and coagulation-related molecules (SERPINB2, PLAU, PLAUR, TFPI, THBD). Serum protein levels for these candidates were measured in a two-step manner in a screening cohort and a validation cohort of pre-PML and NTZ-ctr patients. Only MMP9 was validated and, in pre-PML patients MMP9 protein levels were significantly reduced at baseline compared with NTZ-ctr patients and levels remained lower at later time points during NTZ treatment. INTERPRETATION: The results from this study suggest that the pro-angiogenic factor MMP9 may play a role as biomarker associated with the development of PML in MS patients treated with NTZ. This article is protected by copyright. All rights reserved.
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- 2017
22. Unexpected high multiple sclerosis activity after switching from fingolimod to alemtuzumab
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Bernard-Valnet, Raphaël, primary, Pignolet, Béatrice, additional, Biotti, Damien, additional, Ciron, Jonathan, additional, Lafontan, Jean François, additional, Dumas, Hervé, additional, Bonneville, Fabrice, additional, and Brassat, David, additional
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- 2018
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23. CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model
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Gebauer, Christina, primary, Pignolet, Béatrice, additional, Yshii, Lidia, additional, Mauré, Emilie, additional, Bauer, Jan, additional, and Liblau, Roland, additional
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- 2017
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24. CD62L test at 2 years of natalizumab predicts progressive multifocal leukoencephalopathy
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Pignolet, Béatrice, primary, Schwab, Nicholas, additional, Schneider-Hohendorf, Tilman, additional, Bucciarelli, Florence, additional, Biotti, Damien, additional, Averseng-Peaureaux, Delphine, additional, Outteryck, Olivier, additional, Ongagna, Jean-Claude, additional, de Sèze, Jérôme, additional, Brochet, Bruno, additional, Ouallet, Jean-Christophe, additional, Debouverie, Marc, additional, Pittion, Sophie, additional, Defer, Gilles, additional, Derache, Nathalie, additional, Hautecoeur, Patrick, additional, Tourbah, Ayman, additional, Labauge, Pierre, additional, Castelnovo, Giovanni, additional, Clavelou, Pierre, additional, Berger, Eric, additional, Pelletier, Jean, additional, Rico, Audrey, additional, Zéphir, Hélène, additional, Laplaud, David, additional, Wiertlewski, Sandrine, additional, Camu, William, additional, Thouvenot, Eric, additional, Casez, Olivier, additional, Moreau, Thibault, additional, Fromont, Agnès, additional, Vukusic, Sandra, additional, Papeix, Caroline, additional, Vermersch, Patrick, additional, Comabella, Manuel, additional, Lebrun-Frenay, Christine, additional, Wiendl, Heinz, additional, and Brassat, David, additional
- Published
- 2016
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25. Migration of encephalitogenic CD8 T cells into the central nervous system is dependent on the α4β1-integrin
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Martin‐Blondel, Guillaume, Pignolet, Béatrice, Tietz, Silvia, Yshii, Lidia, Gebauer, Christina, Perinat, Therese, Van Weddingen, Isabelle, Blatti, Claudia, Engelhardt, Britta, and Liblau, Roland
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Mice, Inbred BALB C ,Junctional adhesion molecule‐B ,Brain ,Vascular Cell Adhesion Molecule-1 ,Regular Article ,CD8-Positive T-Lymphocytes ,Integrin alpha4beta1 ,α4β1‐Integrin ,Mice, Inbred C57BL ,Mice ,Neuroinflammation ,Cell Movement ,Animals ,Cellular Immune Response ,Microglia ,Encephalomyelitis ,610 Medicine & health ,Cell Adhesion Molecules ,Migration ,CD8 T cell - Abstract
Although CD8 T cells are key players in neuroinflammation, little is known about their trafficking cues into the central nervous system (CNS). We used a murine model of CNS autoimmunity to define the molecules involved in cytotoxic CD8 T-cell migration into the CNS. Using a panel of mAbs, we here show that the α4β1-integrin is essential for CD8 T-cell interaction with CNS endothelium. We also investigated which α4β1-integrin ligands expressed by endothelial cells are implicated. The blockade of VCAM-1 did not protect against autoimmune encephalomyelitis, and only partly decreased the CD8(+) T-cell infiltration into the CNS. In addition, inhibition of junctional adhesion molecule-B expressed by CNS endothelial cells also decreases CD8 T-cell infiltration. CD8 T cells may use additional and possibly unidentified adhesion molecules to gain access to the CNS.
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- 2015
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26. CTLA4 blockade elicits paraneoplastic neurological disease in a mouse model
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Yshii, Lidia M., primary, Gebauer, Christina M., additional, Pignolet, Béatrice, additional, Mauré, Emilie, additional, Quériault, Clémence, additional, Pierau, Mandy, additional, Saito, Hiromitsu, additional, Suzuki, Noboru, additional, Brunner-Weinzierl, Monika, additional, Bauer, Jan, additional, and Liblau, Roland, additional
- Published
- 2016
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27. Études rétrospective et prospective du CD62L en tant que biomarqueur prédictif du risque de leucoencéphalite multifocale progressive (LEMP) chez les patients sclérose en plaques (SEP) traités par natalizumab (NTZ)
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Pignolet, Béatrice, primary, Biotti, Damien, additional, Brochet, Bruno, additional, Labauge, Pierre, additional, Pelletier, Jean, additional, Lebrun, Christine, additional, and Brassat, David, additional
- Published
- 2016
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28. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values
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Schwab, Nicholas, primary, Schneider-Hohendorf, Tilman, additional, Pignolet, Béatrice, additional, Breuer, Johanna, additional, Gross, Catharina C., additional, Göbel, Kerstin, additional, Brassat, David, additional, and Wiendl, Heinz, additional
- Published
- 2016
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29. Migration of encephalitogenic CD8 T cells into the central nervous system is dependent on the α4β1‐integrin
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Martin‐Blondel, Guillaume, primary, Pignolet, Béatrice, additional, Tietz, Silvia, additional, Yshii, Lidia, additional, Gebauer, Christina, additional, Perinat, Therese, additional, Van Weddingen, Isabelle, additional, Blatti, Claudia, additional, Engelhardt, Britta, additional, and Liblau, Roland, additional
- Published
- 2015
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30. PML risk stratification using anti-JCV antibody index and L-selectin
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Schwab, Nicholas, primary, Schneider-Hohendorf, Tilman, additional, Pignolet, Béatrice, additional, Spadaro, Michela, additional, Görlich, Dennis, additional, Meinl, Ingrid, additional, Windhagen, Susanne, additional, Tackenberg, Björn, additional, Breuer, Johanna, additional, Cantó, Ester, additional, Kümpfel, Tania, additional, Hohlfeld, Reinhard, additional, Siffrin, Volker, additional, Luessi, Felix, additional, Posevitz-Fejfár, Anita, additional, Montalban, Xavier, additional, Meuth, Sven G, additional, Zipp, Frauke, additional, Gold, Ralf, additional, Du Pasquier, Renaud A, additional, Kleinschnitz, Christoph, additional, Jacobi, Annett, additional, Comabella, Manuel, additional, Bertolotto, Antonio, additional, Brassat, David, additional, and Wiendl, Heinz, additional
- Published
- 2015
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31. Migration et pathogénicité des lymphocytes T CD8 dans les maladies du système nerveux central
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Martin-Blondel, Guillaume, primary, Pignolet, Béatrice, additional, and Liblau, Roland S., additional
- Published
- 2015
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32. Spectre de la neuromyélite optique et anticorps anti-MOG
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Biotti, Damien, primary, Mahieu, Laurence, additional, Bernard-Valnet, Raphaël, additional, Peaureaux-Averseng, Delphine, additional, Pignolet, Béatrice, additional, Bucciarelli, Florence, additional, Rabadeux, Céline, additional, Naudin, Aurore, additional, Marignier, Romain, additional, and Brassat, David, additional
- Published
- 2015
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33. Investigation des processus auto-immuns dans la narcolepsie avec cataplexie
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Bernard-Valnet, Raphaël, primary, Queriault, Clémence, additional, Yshii, Lidia, additional, Pignolet, Béatrice, additional, Dauvilliers, Yves, additional, Peyron, Christelle, additional, and Liblau, Roland, additional
- Published
- 2015
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34. Matrix metalloproteinase 9 is decreased in natalizumab-treated multiple sclerosis patients at risk for progressive multifocal leukoencephalopathy.
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Fissolo, Nicolas, Pignolet, Béatrice, Matute‐Blanch, Clara, Triviño, Juan Carlos, Miró, Berta, Mota, Miriam, Perez‐Hoyos, Santiago, Sanchez, Alex, Vermersch, Patrick, Ruet, Aurélie, Sèze, Jérôme, Labauge, Pierre, Vukusic, Sandra, Papeix, Caroline, Almoyna, Laurent, Tourbah, Ayman, Clavelou, Pierre, Moreau, Thibault, Pelletier, Jean, and Lebrun‐Frenay, Christine
- Subjects
- *
MATRIX metalloproteinases , *NATALIZUMAB , *PROGRESSIVE multifocal leukoencephalopathy , *GENE expression , *RNA sequencing - Abstract
Objective: To identify biomarkers associated with the development of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab (NTZ).Methods: Relapsing-remitting MS patients who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr) were included in the study. Cryopreserved peripheral blood mononuclear cells and serum samples collected at baseline, at 1- and 2-year treated time points, and during PML were analyzed for gene expression by RNA sequencing and for serum protein levels by Luminex and enzyme-linked immunosorbent assays, respectively.Results: Among top differentially expressed genes in the RNA sequencing between pre-PML and NTZ-ctr patients, pathway analysis revealed a high representation of genes belonging to the following categories: proangiogenic factors (MMP9, VEGFA), chemokines (CXCL1, CXCL5, IL8, CCL2), cytokines (IL1B, IFNG), and plasminogen- and coagulation-related molecules (SERPINB2, PLAU, PLAUR, TFPI, THBD). Serum protein levels for these candidates were measured in a 2-step manner in a screening cohort and a validation cohort of pre-PML and NTZ-ctr patients. Only matrix metalloproteinase 9 (MMP9) was validated; in pre-PML patients, MMP9 protein levels were significantly reduced at baseline compared with NTZ-ctr patients, and levels remained lower at later time points during NTZ treatment.Interpretation: The results from this study suggest that the proangiogenic factor MMP9 may play a role as a biomarker associated with the development of PML in MS patients treated with NTZ. Ann Neurol 2017;82:186-195. [ABSTRACT FROM AUTHOR]- Published
- 2017
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35. alpha4beta1 is a major molecular cue used by cytotoxic CD8 T cells to migrate into the CNS
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Martin-blondel, Guillaume, primary, Pignolet, Béatrice, additional, Tietz, Silvia, additional, Blatti, Claudia, additional, Perinat, Therese, additional, Yshii, Lidia, additional, Gebauer, Christina, additional, Engelhardt, Britta, additional, and Liblau, Roland, additional
- Published
- 2014
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36. Immunopathogenesis of paraneoplastic neurological syndromes associated with anti-Hu antibodies
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Pignolet, Béatrice SL, primary, Gebauer, Christina MT, additional, and Liblau, Roland S, additional
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- 2013
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37. PML risk stratification using anti-JCV antibody index and L-selectin.
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Schwab, Nicholas, Schneider-Hohendorf, Tilman, Pignolet, Béatrice, Spadaro, Michela, Görlich, Dennis, Meinl, Ingrid, Windhagen, Susanne, Tackenberg, Björn, Breuer, Johanna, Cantó, Ester, Kümpfel, Tania, Hohlfeld, Reinhard, Siffrin, Volker, Luessi, Felix, Posevitz-Fejfár, Anita, Montalban, Xavier, Meuth, Sven G., Zipp, Frauke, Gold, Ralf, and Du Pasquier, Renaud A.
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NATALIZUMAB ,MONOCLONAL antibodies ,ETIOLOGY of diseases ,IMMUNOGLOBULINS ,PATIENTS - Abstract
Background: Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters. Objective: This study aimed at verifying and integrating both parameters into one algorithm for risk stratification. Methods: Multicentric, international cohorts of natalizumab-treated MS patients were assessed for JCV index (1921 control patients and nine pre-PML patients) and CD62L (1410 control patients and 17 pre-PML patients). Results: CD62L values correlate with JCV serostatus, as well as JCV index values. Low CD62L in natalizumab-treated patients was confirmed and validated as a biomarker for PML risk with the risk factor “CD62L low” increasing a patient’s relative risk 55-fold (p < 0.0001). Validation efforts established 86% sensitivity/91% specificity for CD62L and 100% sensitivity/59% specificity for JCV index as predictors of PML. Using both parameters identified 1.9% of natalizumab-treated patients in the reference center as the risk group. Conclusions: Both JCV index and CD62L have merit for risk stratification and share a potential biological relationship with implications for general PML etiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence. [ABSTRACT FROM AUTHOR]
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- 2016
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38. EVER Proteins, Key Elements of the Natural Anti-Human Papillomavirus Barrier, Are Regulated upon T-Cell Activation
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Lazarczyk, Maciej, primary, Dalard, Cécile, additional, Hayder, Myriam, additional, Dupre, Loïc, additional, Pignolet, Béatrice, additional, Majewski, Slawomir, additional, Vuillier, Francoise, additional, Favre, Michel, additional, and Liblau, Roland S., additional
- Published
- 2012
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39. Cutting Edge: Neuronal Recognition by CD8 T Cells Elicits Central Diabetes Insipidus
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Scheikl, Tanja, primary, Pignolet, Béatrice, additional, Dalard, Cécile, additional, Desbois, Sabine, additional, Raison, Danièle, additional, Yamazaki, Masanori, additional, Saoudi, Abdelhadi, additional, Bauer, Jan, additional, Lassmann, Hans, additional, Hardin-Pouzet, Hélène, additional, and Liblau, Roland S., additional
- Published
- 2012
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40. Sclérose en plaques (SEP) : de l’importance de constituer de larges cohortes de patients et de l’intérêt des biomarqueurs notamment génomique : l’exemple du natalizumab (NTZ) chez 1200 patients français
- Author
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Pignolet, Beatrice, Breuil, Norman, Martinez, Maria, Comabella, Manuel, Escorza, Sergio, Wiendl, Heinz, and Brassat, David
- Published
- 2015
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41. Safety and immunogenicity of myxoma virus as a new viral vector for small ruminants
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Pignolet, Béatrice, primary, Boullier, Séverine, additional, Gelfi, Jacqueline, additional, Bozzetti, Marjorie, additional, Russo, Pierre, additional, Foulon, Eliane, additional, Meyer, Gilles, additional, Delverdier, Maxence, additional, Foucras, Gilles, additional, and Bertagnoli, Stéphane, additional
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- 2008
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42. In vitro permissivity of bovine cells for wild-type and vaccinal myxoma virus strains
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Pignolet, Béatrice, primary, Duteyrat, Jean-Luc, additional, Allemandou, Aude, additional, Gelfi, Jacqueline, additional, Foucras, Gilles, additional, and Bertagnoli, Stéphane, additional
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- 2007
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43. A Virulence Factor of Myxoma Virus Colocalizes with NF-κB in the Nucleus and Interferes with Inflammation
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Camus-Bouclainville, Christelle, primary, Fiette, Laurence, additional, Bouchiha, Sophie, additional, Pignolet, Béatrice, additional, Counor, Dorian, additional, Filipe, Cédric, additional, Gelfi, Jacqueline, additional, and Messud-Petit, Frédérique, additional
- Published
- 2004
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44. A mouse model for paraneoplastic neurological syndrome: From anti-tumor immunity to autoimmunity targeting neurons
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Gebauer, Christina, Pignolet, Beatrice, Yshii, Lidia, Martin-blondel, Guillaume, Engelhardt, Britta, Brassat, David, and Liblau, Roland
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- 2014
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45. Vitamin D affects the risk of disease activity in multiple sclerosis.
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Giordano A, Clarelli F, Pignolet B, Mascia E, Sorosina M, Misra K, Ferrè L, Bucciarelli F, Manouchehrinia A, Moiola L, Martinelli V, Rocca MA, Liblau R, Filippi M, and Esposito F
- Abstract
Background: Vitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity., Methods: 230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality., Results: Lower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041)., Conclusions: VitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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46. BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS.
- Author
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Cohen M, Mondot L, Bucciarelli F, Pignolet B, Laplaud DA, Wiertlewski S, Brochet B, Ruet A, Defer G, Derache N, Vermersch P, Zephir H, Debouverie M, Mathey G, Berger E, Cappé C, Labauge P, Carra C, De Seze J, Bigaut K, Brassat D, and Lebrun-Frenay C
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- Humans, Natalizumab therapeutic use, Neoplasm Recurrence, Local, Prospective Studies, Fingolimod Hydrochloride therapeutic use, Multiple Sclerosis
- Abstract
Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS)., Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting MS., Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity., Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029)., Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing-remitting MS. Our results suggest a superiority of NTZ over FTY.
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- 2021
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47. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.
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Ostkamp P, Salmen A, Pignolet B, Görlich D, Andlauer TFM, Schulte-Mecklenbeck A, Gonzalez-Escamilla G, Bucciarelli F, Gennero I, Breuer J, Antony G, Schneider-Hohendorf T, Mykicki N, Bayas A, Then Bergh F, Bittner S, Hartung HP, Friese MA, Linker RA, Luessi F, Lehmann-Horn K, Mühlau M, Paul F, Stangel M, Tackenberg B, Tumani H, Warnke C, Weber F, Wildemann B, Zettl UK, Ziemann U, Müller-Myhsok B, Kümpfel T, Klotz L, Meuth SG, Zipp F, Hemmer B, Hohlfeld R, Brassat D, Gold R, Gross CC, Lukas C, Groppa S, Loser K, Wiendl H, and Schwab N
- Subjects
- B-Lymphocytes radiation effects, Cohort Studies, Female, Genetic Variation, Genotype, Humans, Interferon-beta pharmacology, Interferon-beta therapeutic use, Male, Middle Aged, Monocytes metabolism, Multiple Sclerosis pathology, Multiple Sclerosis radiotherapy, Phenotype, Phototherapy, Recurrence, Severity of Illness Index, Sunlight, T-Lymphocytes metabolism, T-Lymphocytes radiation effects, Transcriptome genetics, Monocytes radiation effects, Multiple Sclerosis blood, Multiple Sclerosis immunology, Receptor, Melanocortin, Type 1 genetics, Transcriptome radiation effects, Vitamin D blood
- Abstract
Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies ( n
NationMS = 946, nBIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β-treated patients. In carriers of MC1R :rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS., Competing Interests: Competing interest statement: H.W. received honoraria and consultation fees from Bayer Healthcare, Biogen, Fresenius Medical Care, GlaxoSmithKline, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi Genzyme, and Teva Pharma. K.L. is coinventor on patent no. US 2016/0158322 A1 entitled “NDP-MSH for treatment of inflammatory and/or neurodegenerative disorders of the CNS.” A.S. received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, none related to this work. R.G. serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd. (Teva), Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva, Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases, and is on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva, Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this work. L.K. receives honoraria for lecturing and travel expenses for attending meetings from Biogen, Merck, Sanofi Genzyme, Novartis and Roche; her research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Interdisciplinary Center for Clinical Studies (IZKF) Muenster, Biogen, Merck, and Novartis. M.A.F. received honoraria for consultation and travel expenses from Biogen, Merck KGaA, Novartis, and Roche; his research is funded by the BMBF, DFG, Landesforschungsförderung Hamburg, Gemeinnützige Hertie-Stiftung, and Else Kröner-Fresenius-Stiftung. S.G.M. receives honoraria for lecturing, and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva; his research is funded by the BMBF, DFG, Else Kröner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, IZKF Muenster, German Foundation Neurology and Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. R.H. has received grant support from Biogen, Genzyme-Sanofi, Merck Serono, Novartis, Teva, and personal fees from Actelion, Biogen, Genzyme-Sanofi, Medday, Merck Serono, Novartis, Roche, and Teva. T.K. has received travel expenses and personal compensation from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche, and Biogen, as well as grant support from Bayer Schering AG, Novartis, and Chugai Pharma. U.Z. has received grants from DFG, BMBF, the European Research Council, Bristol Myers Squibb, Janssen Pharmaceuticals NV, Servier, and Biogen Idec, and personal consultation fees from Pfizer GmbH, Bayer Vital GmbH, and CorTec GmbH. F.Z. received funds for scientific consultation or research by DFG, BMBF, the Pharmaceutical Management Science Association, Novartis, Octapharma, Merck Serono, ONO Pharma, Biogen, Genzyme, Celgene, Roche, Sanofi Aventis. A.S.-M. received travel expenses and research support from Novartis. C.C.G. received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, MyLan, Novartis Pharma GmbH, and Bayer Health Care, none related to this study; her work is funded by Biogen, Novartis, the BMBF (01Gl1603A), the DFG (GR3946/3-1, SFB Transregio 128 A09), the European Union (Horizon2020, ReSToRE), the IZKF, and the Innovative Medizinische Forschung. D.B. receives lectures, congress invitation, board participation with Bayer, Biogen, Medday, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. B.T. received personal speaker honoraria and consultancy fees as a speaker and advisor from Alexion, Bayer Healthcare, Biogen, CSL Behring, GILEAD, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, Teva, and UCB Pharma; his university received unrestricted research grants from Biogen-Idec, Novartis, Teva, Bayer Healthcare, CSL-Behring, GRIFOLS, Octapharma, Sanofi Genzyme, and UCB Pharma. F.T.B. has received, through his institution, grant support and/or travel reimbursement to attend scientific meetings from Actelion, Bayer, Biogen, Merck, Novartis, Sanofi Genzyme, and Teva; he has received personal honoraria for speaking or advisory board activities from Actelion, Bayer, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme; his research is funded, in part, by the DFG and the BMBF. C.W. has received institutional support from Novartis, Sanofi Genzyme, Biogen, and Roche. H.-P.H. has received fees for consulting, speaking, and serving on steering committees from Bayer Healthcare, Biogen, GeNeuro, MedImmune, Merck, Novartis, Opexa, Receptos Celgene, Roche, Sanofi Genzyme, CSL Behring, Octapharma, and Teva, with approval by the Rector of Heinrich-Heine University. H.T. received speaker honoraria from Bayer, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche, Siemens, and Teva; he serves as section editor for the Journal of Neurology, Psychiatry, and Brain Research; H.T. and his institution receives research support from the BMBF, DMSG, Fresenius, Genzyme, Merck, and Novartis, none related to this work. A.B. has received personal compensation from Merck, Biogen, Bayer Vital, Novartis, Teva, Roche, Celgene, Alexion, and Sanofi Genzyme, and grants for congress trips and participation from Biogen, Teva, Novartis, Sanofi Genzyme, Celgene, and Merck, none related to this work. C.L. received an endowed professorship supported by the Novartis foundation, has received consulting and speaker’s honoraria from Biogen-Idec, Bayer Schering, Novartis, Sanofi Genzyme, and Teva; and has received research scientific grant support from Merck-Serono and Novartis. B.W. received research grants and/or honoria from Merck Serono, Biogen, Teva, Novartis, Sanofi Genzyme, Bayer Healthcare, Roche, and research grants from the Dietmar Hopp Foundation, the Klaus Tschira Foundation, the BMBF, and the DFG. U.K.Z. received honoraria for lecturing and/or travel expenses for attending meetings from Almirall, Alexion, Bayer, Biogen, Celgene, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, and Teva, as well as grant support from the BMBF and European Union, none related to this study; his research is funded by the BMBF, German Ministry of Economy, DFG, and European Union. S.B. has received honoria and compensation for travel from Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, and Roche. M.S. has received honoraria for scientific lectures or consultancy from Alexion, Bayer Healthcare, Biogen, CSL Behring, Grifols, MedDay, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva; his institution received research support from Biogen, Sanofi-Genzyme, and Merck-Serono. R.A.L. received personal compensation from Celgene, Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche, and Biogen, as well as grant support from Novartis and Merck. F.W. served on the scientific advisory board of Genzyme, Merck Serono, and Novartis; he has received travel funding and/or speaker honoraria from Bayer, Biogen, Teva, Merck Serono, Novartis, and Pfizer; he is employed by Sana and received research support from the BMBF, Merck Serono, and Novartis. F.P. reported other support from Bayer, Novartis, Biogen-Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, Roche, and Shire outside the submitted work; he has a post as academic editor for PLoS One and is associate editor for Neurology: Neuroimmunology & Neuroinflammation; he has scientific advisory board membership for Novartis and consulting fees from Sanofi Genzyme, Biogen-Idec, MedImmune, Shire, and Alexion; and research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, the German Research Council, Werth Stiftung, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the United States. B.H. has served on scientific advisory boards for Novartis; he has served as data monitoring and safety committee member for AllergyCare and TG therapeutics; he or his institution have received speaker honoraria from Desitin; he holds part of two patents, one for the detection of antibodies against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon. All conflicts are not relevant to the topic of the study. F.L. has served on the advisory board of Roche and received travel funding from Teva. M.M. received research support from Merck Serono and Novartis as well as travel expenses for attending meetings from Merck Serono. K.L.-H. has received research support (to Technische Universität München) from Novartis, honoraria from Novartis and F. Hoffmann-La Roche, and compensation for travel expenses from Merck Serono., (Copyright © 2021 the Author(s). Published by PNAS.)- Published
- 2021
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48. CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model.
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Gebauer C, Pignolet B, Yshii L, Mauré E, Bauer J, and Liblau R
- Abstract
Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins. However, its precise contribution in the pathogenesis remains unclear. In this context, our study aimed at investigating the impact of anti-tumor cellular immune responses in the development of PND. To this end, we developed an animal model mimicking PND. We used a tumor cell line expressing the hemagglutinin (HA) of influenza virus to induce an anti-tumor response in CamK-HA mice, which express HA in CNS neurons. To promote and track the T cell response against the HA antigen, naïve HA-specific CD8+ and/or CD4+ T cells, originating from TCR-transgenic animals, were transferred into these mice. We demonstrate that HA-expressing tumors, but not control tumors, induce in vivo activation, proliferation and differentiation of naïve HA-specific CD4+ and CD8+ T cells into effector cells. Moreover, both T cell subsets were needed to control tumor growth and induce CNS inflammation in CamK-HA mice. Thus, this new mouse model provides further insight into the cellular mechanisms whereby a potent anti-tumor immunity triggers a cancer-associated autoimmune disease, and may therefore help to develop new therapeutic strategies against PND.
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- 2016
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49. PML risk stratification using anti-JCV antibody index and L-selectin.
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Schwab N, Schneider-Hohendorf T, Pignolet B, Spadaro M, Görlich D, Meinl I, Windhagen S, Tackenberg B, Breuer J, Cantó E, Kümpfel T, Hohlfeld R, Siffrin V, Luessi F, Posevitz-Fejfár A, Montalban X, Meuth SG, Zipp F, Gold R, Du Pasquier RA, Kleinschnitz C, Jacobi A, Comabella M, Bertolotto A, Brassat D, and Wiendl H
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- Algorithms, Biomarkers blood, Europe, Humans, Immunocompromised Host, Leukoencephalopathy, Progressive Multifocal immunology, Leukoencephalopathy, Progressive Multifocal prevention & control, Leukoencephalopathy, Progressive Multifocal virology, Multiple Sclerosis blood, Multiple Sclerosis diagnosis, Multiple Sclerosis immunology, Opportunistic Infections immunology, Opportunistic Infections virology, Retrospective Studies, Risk Assessment, Risk Factors, Serologic Tests, Treatment Outcome, Antibodies, Viral blood, JC Virus immunology, L-Selectin blood, Leukoencephalopathy, Progressive Multifocal chemically induced, Multiple Sclerosis drug therapy, Natalizumab adverse effects, Opportunistic Infections chemically induced
- Abstract
Background: Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters., Objective: This study aimed at verifying and integrating both parameters into one algorithm for risk stratification., Methods: Multicentric, international cohorts of natalizumab-treated MS patients were assessed for JCV index (1921 control patients and nine pre-PML patients) and CD62L (1410 control patients and 17 pre-PML patients)., Results: CD62L values correlate with JCV serostatus, as well as JCV index values. Low CD62L in natalizumab-treated patients was confirmed and validated as a biomarker for PML risk with the risk factor "CD62L low" increasing a patient's relative risk 55-fold (p < 0.0001). Validation efforts established 86% sensitivity/91% specificity for CD62L and 100% sensitivity/59% specificity for JCV index as predictors of PML. Using both parameters identified 1.9% of natalizumab-treated patients in the reference center as the risk group., Conclusions: Both JCV index and CD62L have merit for risk stratification and share a potential biological relationship with implications for general PML etiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence., (© The Author(s), 2015.)
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- 2016
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50. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values.
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Schwab N, Schneider-Hohendorf T, Pignolet B, Breuer J, Gross CC, Göbel K, Brassat D, and Wiendl H
- Abstract
Objective: The aim of the study was to analyze John Cunningham virus (JCV) serology in natalizumab-treated patients over time and assess whether they are influenced by natalizumab treatment., Methods: German (n = 1,921; 525 longitudinally) and French (n = 1,259; 711 longitudinally) patients were assessed for JCV serology alongside their therapy with natalizumab., Results: JCV serostatus changed in 69 of 525 longitudinally followed German patients (13.1%) over 14.8 months. Seroconversion according to serostatus was seen in 43 of 339 initially JCV- German patients (12.7% in 14.8 months; 10.3% per year) and 41 of 243 initially JCV- French patients (16.9% in 24 months; 8.5% per year). JCV index values could be reproduced (R (2) = 0.89) with the caveat of 8 of 50 samples (16%) being set into different risk categories between 2 assessments. Index values of JCV+ patients rose over time (p = 0.009) but not because of aging. Treatment with natalizumab was associated with a 15.9% increase of value in JCV+ patients in 14.8 months (12.9% per year)., Conclusions: JCV seroconversion and index values may be influenced by treatment with natalizumab. It is therefore important to monitor patients' JCV serology but also to incorporate additional risk factors into the progressive multifocal leukoencephalopathy risk stratification.
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- 2016
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