HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in context
Summary: Background: Glatiramer acetate (GA) is a well-tolerated treatment for multiple sclerosis (MS) and comparable in its efficacy to high-dose interferon beta (IFN). As a lack of validated treatment response biomarkers for MS hampers progress in personalised treatment, the study goal was to sea...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425003172 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849399265077493760 |
|---|---|
| author | Brian C. Zhang Tilman Schneider-Hohendorf Rebecca Elyanow Beatrice Pignolet Simon Falk Christian Wünsch Marie Deffner Erik Yusko Damon May Daniel Mattox Eva Dawin Lisa Ann Gerdes Florence Bucciarelli Lisa Revie Gisela Antony Sven Jarius Christiane Seidel Makbule Senel Stefan Bittner Felix Luessi Joachim Havla Matthias Knop Manuel A. Friese Susanne Rothacher Anke Salmen Fumie Hayashi Roland Henry Stacy Caillier Adam Santaniello Maria Seipelt Christoph Heesen Sandra Nischwitz Antonios Bayas Hayrettin Tumani Florian Then Bergh Gerd Meyer zu Hörste Tania Kümpfel Catharina C. Gross Brigitte Wildemann Martin Kerschensteiner Ralf Gold Sven G. Meuth Frauke Zipp Bruce A.C. Cree Jorge Oksenberg Michael R. Wilson Stephen L. Hauser Scott S. Zamvil Luisa Klotz Roland Liblau Harlan Robins Joseph J. Sabatino, Jr. Heinz Wiendl Nicholas Schwab Jessa Alexander Riley Bove Sergio Baranzini Bruce A.C. Cree Eduardo Caverzasi Richard Cuneo Stacy J. Caillier Tiffany Cooper Ari J. Green Chu-Yueh Guo Jeffrey M. Gelfand Refujia Gomez Sasha Gupta Jill Hollenbach Meagan Harms Roland G. Henry Stephen L. Hauser Myra Mendoza Jorge R. Oksenberg Nico Papinutto Sam Pleasure Adam Santaniello Joseph J. Sabatino, Jr. William A. Stern Michael R. Wilson Scott Zamvil Orhan Aktas Antje Giede-Jeppe Barbara Gisevius Markus Kowarik Friedemann Paul Veit Rothhammer Corinna Trebst Uwe Zettl |
| author_facet | Brian C. Zhang Tilman Schneider-Hohendorf Rebecca Elyanow Beatrice Pignolet Simon Falk Christian Wünsch Marie Deffner Erik Yusko Damon May Daniel Mattox Eva Dawin Lisa Ann Gerdes Florence Bucciarelli Lisa Revie Gisela Antony Sven Jarius Christiane Seidel Makbule Senel Stefan Bittner Felix Luessi Joachim Havla Matthias Knop Manuel A. Friese Susanne Rothacher Anke Salmen Fumie Hayashi Roland Henry Stacy Caillier Adam Santaniello Maria Seipelt Christoph Heesen Sandra Nischwitz Antonios Bayas Hayrettin Tumani Florian Then Bergh Gerd Meyer zu Hörste Tania Kümpfel Catharina C. Gross Brigitte Wildemann Martin Kerschensteiner Ralf Gold Sven G. Meuth Frauke Zipp Bruce A.C. Cree Jorge Oksenberg Michael R. Wilson Stephen L. Hauser Scott S. Zamvil Luisa Klotz Roland Liblau Harlan Robins Joseph J. Sabatino, Jr. Heinz Wiendl Nicholas Schwab Jessa Alexander Riley Bove Sergio Baranzini Bruce A.C. Cree Eduardo Caverzasi Richard Cuneo Stacy J. Caillier Tiffany Cooper Ari J. Green Chu-Yueh Guo Jeffrey M. Gelfand Refujia Gomez Sasha Gupta Jill Hollenbach Meagan Harms Roland G. Henry Stephen L. Hauser Myra Mendoza Jorge R. Oksenberg Nico Papinutto Sam Pleasure Adam Santaniello Joseph J. Sabatino, Jr. William A. Stern Michael R. Wilson Scott Zamvil Orhan Aktas Antje Giede-Jeppe Barbara Gisevius Markus Kowarik Friedemann Paul Veit Rothhammer Corinna Trebst Uwe Zettl |
| author_sort | Brian C. Zhang |
| collection | DOAJ |
| description | Summary: Background: Glatiramer acetate (GA) is a well-tolerated treatment for multiple sclerosis (MS) and comparable in its efficacy to high-dose interferon beta (IFN). As a lack of validated treatment response biomarkers for MS hampers progress in personalised treatment, the study goal was to search for biomarkers of a successful treatment response utilising the known observation of T-cell expansions after GA treatment. Methods: T-cell receptor beta chain (TRB) sequencing was performed in 3021 patients with MS: a discovery cohort of 1627 patients with MS, 204 of whom had previously been treated with GA, and then validated in 1394 patients with MS, 424 of whom had previously been treated with GA. Clinical data from 1987 patients with MS treated with GA or IFN and available HLA information from the NationMS, ACP, EPIC, BIONAT, and CombiRx trial cohorts were used for a subsequent analysis. Findings: Common GA-associated TRB expansions were exclusively detected in HLA-A∗03:01 or in HLA-DRB1∗15:01 backgrounds, within CD8+ effector- or CD4+ central-memory T cells. Both sets of common sequences clonally expanded after GA treatment in a first validation cohort and predicted GA exposure in two further validation cohorts. To evaluate whether restriction of public TRBs to only two HLA alleles is also associated with GA’s clinical efficacy, we analysed five cohorts of patients with MS for a potential benefit of the two HLAs concerning the GA response compared to IFN. We consistently found positive interactions with HLA-A∗03:01. This included a relative reduction in relapse risk compared to IFN in HLA-A∗03:01 carriers of 33% (CombiRx: GA + IFN arm: HR 0.67 [95% CI: 0.47–0.96], p = 0.0269) and 34% (CombiRx: GA arm: HR 0.66 [95% CI: 0.45–0.98], p = 0.0377), and in risk to first relapse of 63% (NationMS: HR 0.37 [95% CI: 0.16–0.88], p = 0.0246), but no positive association with DRB1∗15:01. Interpretation: HLA-A∗03:01 carrying patients with MS specifically benefit from GA treatment and GA significantly outperforms IFN in these patients. Therefore, determining HLA-A∗03:01 status before choosing a platform treatment for MS, would allow for a personalised treatment decision between GA and IFN. Funding: German Research Foundation, National Institutes of Health, National Multiple Sclerosis Society, Valhalla Foundation, Westridge Foundation, Mayer Foundation, German Federal Ministry of Education and Research. |
| format | Article |
| id | doaj-art-2b2aec6e24434ccc858da6d2835cdaa0 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-2b2aec6e24434ccc858da6d2835cdaa02025-08-20T03:38:23ZengElsevierEBioMedicine2352-39642025-08-0111810587310.1016/j.ebiom.2025.105873HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in contextBrian C. Zhang0Tilman Schneider-Hohendorf1Rebecca Elyanow2Beatrice Pignolet3Simon Falk4Christian Wünsch5Marie Deffner6Erik Yusko7Damon May8Daniel Mattox9Eva Dawin10Lisa Ann Gerdes11Florence Bucciarelli12Lisa Revie13Gisela Antony14Sven Jarius15Christiane Seidel16Makbule Senel17Stefan Bittner18Felix Luessi19Joachim Havla20Matthias Knop21Manuel A. Friese22Susanne Rothacher23Anke Salmen24Fumie Hayashi25Roland Henry26Stacy Caillier27Adam Santaniello28Maria Seipelt29Christoph Heesen30Sandra Nischwitz31Antonios Bayas32Hayrettin Tumani33Florian Then Bergh34Gerd Meyer zu Hörste35Tania Kümpfel36Catharina C. Gross37Brigitte Wildemann38Martin Kerschensteiner39Ralf Gold40Sven G. Meuth41Frauke Zipp42Bruce A.C. Cree43Jorge Oksenberg44Michael R. Wilson45Stephen L. Hauser46Scott S. Zamvil47Luisa Klotz48Roland Liblau49Harlan Robins50Joseph J. Sabatino, Jr.51Heinz Wiendl52Nicholas Schwab53Jessa AlexanderRiley BoveSergio BaranziniBruce A.C. CreeEduardo CaverzasiRichard CuneoStacy J. CaillierTiffany CooperAri J. GreenChu-Yueh GuoJeffrey M. GelfandRefujia GomezSasha GuptaJill HollenbachMeagan HarmsRoland G. HenryStephen L. HauserMyra MendozaJorge R. OksenbergNico PapinuttoSam PleasureAdam SantanielloJoseph J. Sabatino, Jr.William A. SternMichael R. WilsonScott ZamvilOrhan AktasAntje Giede-JeppeBarbara GiseviusMarkus KowarikFriedemann PaulVeit RothhammerCorinna TrebstUwe ZettlAdaptive Biotechnologies, Seattle, WA, USADepartment of Neurology, University of Muenster, Muenster, GermanyAdaptive Biotechnologies, Seattle, WA, USAToulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, Toulouse, FranceDepartment of Neurology, University of Muenster, Muenster, GermanyDepartment of Neurology, University of Muenster, Muenster, GermanyDepartment of Neurology, University of Muenster, Muenster, GermanyAdaptive Biotechnologies, Seattle, WA, USAAdaptive Biotechnologies, Seattle, WA, USAAdaptive Biotechnologies, Seattle, WA, USADepartment of Neurology, University of Muenster, Muenster, GermanyInstitute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University Munich, Munich, Germany; Biomedical Center, Faculty of Medicine, Ludwig Maximilian University Munich, Martinsried, Germany; Munich Cluster of Systems Neurology (SyNergy), Munich, GermanyToulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, Toulouse, FranceDepartment of Neurology, University of Muenster, Muenster, GermanyCentral Information Office German Competence Network of Multiple Sclerosis, Philipps University Marburg, Marburg, GermanyDepartment of Neurology, University of Heidelberg, Heidelberg, GermanyDepartment of Neurology, University of Leipzig, Leipzig, GermanyDepartment of Neurology, University of Ulm, Ulm, GermanyDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyInstitute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University Munich, Munich, GermanyMax Planck Institute of Psychiatry, Munich, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, GermanyDepartment of Neurology and Clinical Neurophysiology, Medical Faculty, University of Augsburg, Augsburg, GermanyDepartment of Neurology, St. Josef-hospital, Ruhr-University Bochum, Bochum, GermanyWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartment of Neurology, University Hospital Marburg, Philipps-University Marburg, Marburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, GermanyMax Planck Institute of Psychiatry, Munich, GermanyDepartment of Neurology and Clinical Neurophysiology, Medical Faculty, University of Augsburg, Augsburg, GermanyDepartment of Neurology, University of Ulm, Ulm, GermanyDepartment of Neurology, University of Leipzig, Leipzig, GermanyDepartment of Neurology, University of Muenster, Muenster, GermanyInstitute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University Munich, Munich, GermanyDepartment of Neurology, University of Muenster, Muenster, GermanyDepartment of Neurology, University of Heidelberg, Heidelberg, GermanyInstitute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University Munich, Munich, Germany; Biomedical Center, Faculty of Medicine, Ludwig Maximilian University Munich, Martinsried, Germany; Munich Cluster of Systems Neurology (SyNergy), Munich, GermanyDepartment of Neurology, St. Josef-hospital, Ruhr-University Bochum, Bochum, GermanyDepartment of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartment of Neurology, University of Muenster, Muenster, GermanyToulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, Toulouse, FranceAdaptive Biotechnologies, Seattle, WA, USAWell Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartment of Neurology, University of Muenster, Muenster, Germany; Department of Neurology and Neurophysiology, University of Freiburg, Freiburg, GermanyDepartment of Neurology, University of Muenster, Muenster, Germany; Corresponding author. Body & Brain Institute Münster, Domagkstraße 24, Muenster 48149, Germany.Summary: Background: Glatiramer acetate (GA) is a well-tolerated treatment for multiple sclerosis (MS) and comparable in its efficacy to high-dose interferon beta (IFN). As a lack of validated treatment response biomarkers for MS hampers progress in personalised treatment, the study goal was to search for biomarkers of a successful treatment response utilising the known observation of T-cell expansions after GA treatment. Methods: T-cell receptor beta chain (TRB) sequencing was performed in 3021 patients with MS: a discovery cohort of 1627 patients with MS, 204 of whom had previously been treated with GA, and then validated in 1394 patients with MS, 424 of whom had previously been treated with GA. Clinical data from 1987 patients with MS treated with GA or IFN and available HLA information from the NationMS, ACP, EPIC, BIONAT, and CombiRx trial cohorts were used for a subsequent analysis. Findings: Common GA-associated TRB expansions were exclusively detected in HLA-A∗03:01 or in HLA-DRB1∗15:01 backgrounds, within CD8+ effector- or CD4+ central-memory T cells. Both sets of common sequences clonally expanded after GA treatment in a first validation cohort and predicted GA exposure in two further validation cohorts. To evaluate whether restriction of public TRBs to only two HLA alleles is also associated with GA’s clinical efficacy, we analysed five cohorts of patients with MS for a potential benefit of the two HLAs concerning the GA response compared to IFN. We consistently found positive interactions with HLA-A∗03:01. This included a relative reduction in relapse risk compared to IFN in HLA-A∗03:01 carriers of 33% (CombiRx: GA + IFN arm: HR 0.67 [95% CI: 0.47–0.96], p = 0.0269) and 34% (CombiRx: GA arm: HR 0.66 [95% CI: 0.45–0.98], p = 0.0377), and in risk to first relapse of 63% (NationMS: HR 0.37 [95% CI: 0.16–0.88], p = 0.0246), but no positive association with DRB1∗15:01. Interpretation: HLA-A∗03:01 carrying patients with MS specifically benefit from GA treatment and GA significantly outperforms IFN in these patients. Therefore, determining HLA-A∗03:01 status before choosing a platform treatment for MS, would allow for a personalised treatment decision between GA and IFN. Funding: German Research Foundation, National Institutes of Health, National Multiple Sclerosis Society, Valhalla Foundation, Westridge Foundation, Mayer Foundation, German Federal Ministry of Education and Research.http://www.sciencedirect.com/science/article/pii/S2352396425003172Glatiramer acetateMultiple sclerosisBiomarkerTreatment responseHLAGenetics |
| spellingShingle | Brian C. Zhang Tilman Schneider-Hohendorf Rebecca Elyanow Beatrice Pignolet Simon Falk Christian Wünsch Marie Deffner Erik Yusko Damon May Daniel Mattox Eva Dawin Lisa Ann Gerdes Florence Bucciarelli Lisa Revie Gisela Antony Sven Jarius Christiane Seidel Makbule Senel Stefan Bittner Felix Luessi Joachim Havla Matthias Knop Manuel A. Friese Susanne Rothacher Anke Salmen Fumie Hayashi Roland Henry Stacy Caillier Adam Santaniello Maria Seipelt Christoph Heesen Sandra Nischwitz Antonios Bayas Hayrettin Tumani Florian Then Bergh Gerd Meyer zu Hörste Tania Kümpfel Catharina C. Gross Brigitte Wildemann Martin Kerschensteiner Ralf Gold Sven G. Meuth Frauke Zipp Bruce A.C. Cree Jorge Oksenberg Michael R. Wilson Stephen L. Hauser Scott S. Zamvil Luisa Klotz Roland Liblau Harlan Robins Joseph J. Sabatino, Jr. Heinz Wiendl Nicholas Schwab Jessa Alexander Riley Bove Sergio Baranzini Bruce A.C. Cree Eduardo Caverzasi Richard Cuneo Stacy J. Caillier Tiffany Cooper Ari J. Green Chu-Yueh Guo Jeffrey M. Gelfand Refujia Gomez Sasha Gupta Jill Hollenbach Meagan Harms Roland G. Henry Stephen L. Hauser Myra Mendoza Jorge R. Oksenberg Nico Papinutto Sam Pleasure Adam Santaniello Joseph J. Sabatino, Jr. William A. Stern Michael R. Wilson Scott Zamvil Orhan Aktas Antje Giede-Jeppe Barbara Gisevius Markus Kowarik Friedemann Paul Veit Rothhammer Corinna Trebst Uwe Zettl HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in context EBioMedicine Glatiramer acetate Multiple sclerosis Biomarker Treatment response HLA Genetics |
| title | HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in context |
| title_full | HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in context |
| title_fullStr | HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in context |
| title_full_unstemmed | HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in context |
| title_short | HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysisResearch in context |
| title_sort | hla a∗03 01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis a retrospective cohort analysisresearch in context |
| topic | Glatiramer acetate Multiple sclerosis Biomarker Treatment response HLA Genetics |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425003172 |
| work_keys_str_mv | AT brianczhang hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT tilmanschneiderhohendorf hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT rebeccaelyanow hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT beatricepignolet hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT simonfalk hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT christianwunsch hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT mariedeffner hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT erikyusko hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT damonmay hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT danielmattox hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT evadawin hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT lisaanngerdes hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT florencebucciarelli hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT lisarevie hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT giselaantony hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT svenjarius hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT christianeseidel hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT makbulesenel hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT stefanbittner hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT felixluessi hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT joachimhavla hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT matthiasknop hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT manuelafriese hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT susannerothacher hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT ankesalmen hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT fumiehayashi hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT rolandhenry hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT stacycaillier hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT adamsantaniello hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT mariaseipelt hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT christophheesen hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT sandranischwitz hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT antoniosbayas hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT hayrettintumani hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT florianthenbergh hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT gerdmeyerzuhorste hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT taniakumpfel hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT catharinacgross hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT brigittewildemann hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT martinkerschensteiner hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT ralfgold hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT svengmeuth hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT fraukezipp hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT bruceaccree hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT jorgeoksenberg hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT michaelrwilson hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT stephenlhauser hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT scottszamvil hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT luisaklotz hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT rolandliblau hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT harlanrobins hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT josephjsabatinojr hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT heinzwiendl hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT nicholasschwab hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT jessaalexander hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT rileybove hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT sergiobaranzini hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT bruceaccree hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT eduardocaverzasi hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT richardcuneo hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT stacyjcaillier hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT tiffanycooper hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT arijgreen hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT chuyuehguo hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT jeffreymgelfand hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT refujiagomez hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT sashagupta hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT jillhollenbach hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT meaganharms hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT rolandghenry hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT stephenlhauser hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT myramendoza hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT jorgeroksenberg hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT nicopapinutto hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT sampleasure hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT adamsantaniello hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT josephjsabatinojr hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT williamastern hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT michaelrwilson hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT scottzamvil hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT orhanaktas hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT antjegiedejeppe hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT barbaragisevius hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT markuskowarik hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT friedemannpaul hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT veitrothhammer hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT corinnatrebst hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext AT uwezettl hlaa0301aspredictivegeneticbiomarkerforglatirameracetatetreatmentresponseinmultiplesclerosisaretrospectivecohortanalysisresearchincontext |