Pascal Benkert PhD, Aleksandra Maleska Maceski MSc, Sabine Schaedelin MSc, Johanna Oechtering MD, Amar Zadic MSc, Juan Francisco Vilchez Gomez MSc, Lester Melie-Garcia PhD, Alessandro Cagol MD, Riccardo Galbusera MD, Suvitha Subramaniam MSc, Johannes Lorscheider MD, Edoardo Galli MD, Jannis Mueller MD, Bettina Fischer-Barnicol MD, Lutz Achtnichts MD, Oliver Findling MD, Patrice H. Lalive MD, Claire Bridel MD, PhD, Marjolaine Uginet MD, Stefanie Müller MD, Caroline Pot MD, Amandine Mathias PhD, Renaud Du Pasquier MD, Anke Salmen MD, Robert Hoepner MD, Andrew Chan MD, Giulio Disanto MD, PhD, Chiara Zecca MD, Marcus D'Souza MD, Lars G. Hemkens MD, Özgür Yaldizli MD, Tobias Derfuss MD, Patrick Roth MD, Claudio Gobbi MD, David Brassat MD, Björn Tackenberg MD, Rosetta Pedotti MD, Catarina Raposo PhD, Jorge Oksenberg PhD, Heinz Wiendl MD, Klaus Berger PhD, Marco Hermesdorf PhD, Fredrik Piehl MD, David Conen MD, Andreas Buser MD, Ludwig Kappos MD, Michael Khalil MD, PhD, Cristina Granziera MD, PhD, Ahmed Abdelhak MD, David Leppert MD, Eline A.J. Willemse PhD, Jens Kuhle MD, PhD, for the Swiss MS Cohort study (SMSC)
{"title":"血清胶质纤维酸性蛋白和神经丝蛋白轻链水平反映多发性硬化症患者在B细胞耗竭治疗下疾病进展的不同机制","authors":"Pascal Benkert PhD, Aleksandra Maleska Maceski MSc, Sabine Schaedelin MSc, Johanna Oechtering MD, Amar Zadic MSc, Juan Francisco Vilchez Gomez MSc, Lester Melie-Garcia PhD, Alessandro Cagol MD, Riccardo Galbusera MD, Suvitha Subramaniam MSc, Johannes Lorscheider MD, Edoardo Galli MD, Jannis Mueller MD, Bettina Fischer-Barnicol MD, Lutz Achtnichts MD, Oliver Findling MD, Patrice H. Lalive MD, Claire Bridel MD, PhD, Marjolaine Uginet MD, Stefanie Müller MD, Caroline Pot MD, Amandine Mathias PhD, Renaud Du Pasquier MD, Anke Salmen MD, Robert Hoepner MD, Andrew Chan MD, Giulio Disanto MD, PhD, Chiara Zecca MD, Marcus D'Souza MD, Lars G. Hemkens MD, Özgür Yaldizli MD, Tobias Derfuss MD, Patrick Roth MD, Claudio Gobbi MD, David Brassat MD, Björn Tackenberg MD, Rosetta Pedotti MD, Catarina Raposo PhD, Jorge Oksenberg PhD, Heinz Wiendl MD, Klaus Berger PhD, Marco Hermesdorf PhD, Fredrik Piehl MD, David Conen MD, Andreas Buser MD, Ludwig Kappos MD, Michael Khalil MD, PhD, Cristina Granziera MD, PhD, Ahmed Abdelhak MD, David Leppert MD, Eline A.J. Willemse PhD, Jens Kuhle MD, PhD, for the Swiss MS Cohort study (SMSC)","doi":"10.1002/ana.27096","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Elevated sGFAP levels (Z score >1) at 1 year were associated with a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17–2.78]; <i>p</i> = 0.0079) than elevated sNfL levels (HR, 1.45 [0.95–2.24], <i>p</i> = 0.0886) in a combined model. Independent of PIRA events, sGFAP levels longitudinally increased by 0.49 Z score units per 10 years follow-up (estimate, 0.49 [0.29, 0.69], <i>p</i> < 0.0001). In patients experiencing PIRA, sGFAP Z scores were 0.52 Z score units higher versus stable patients (0.52 [0.22, 0.83], <i>p</i> = 0.0009). Different sNfL Z score trajectories were found in pwMS with versus without PIRA (interaction <i>p</i> = 0.0028), with an average decrease of 0.92 Z score units per 10 years observed without PIRA (−0.92 [−1.23, −0.60], <i>p</i> < 0.0001), whereas levels in patients with PIRA remained high.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>Elevated sGFAP and lack of drop in sNfL after BCDT start are associated with increased risk of future PIRA. These findings provide a rationale for combined monitoring of sNfL and sGFAP in pwMS starting BCDT to predict the risk of PIRA, and to use sGFAP as an outcome in clinical trials aiming to impact on MS progressive disease biology. ANN NEUROL 2025;97:104–115</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"104-115"},"PeriodicalIF":8.1000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683165/pdf/","citationCount":"0","resultStr":"{\"title\":\"Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis\",\"authors\":\"Pascal Benkert PhD, Aleksandra Maleska Maceski MSc, Sabine Schaedelin MSc, Johanna Oechtering MD, Amar Zadic MSc, Juan Francisco Vilchez Gomez MSc, Lester Melie-Garcia PhD, Alessandro Cagol MD, Riccardo Galbusera MD, Suvitha Subramaniam MSc, Johannes Lorscheider MD, Edoardo Galli MD, Jannis Mueller MD, Bettina Fischer-Barnicol MD, Lutz Achtnichts MD, Oliver Findling MD, Patrice H. Lalive MD, Claire Bridel MD, PhD, Marjolaine Uginet MD, Stefanie Müller MD, Caroline Pot MD, Amandine Mathias PhD, Renaud Du Pasquier MD, Anke Salmen MD, Robert Hoepner MD, Andrew Chan MD, Giulio Disanto MD, PhD, Chiara Zecca MD, Marcus D'Souza MD, Lars G. Hemkens MD, Özgür Yaldizli MD, Tobias Derfuss MD, Patrick Roth MD, Claudio Gobbi MD, David Brassat MD, Björn Tackenberg MD, Rosetta Pedotti MD, Catarina Raposo PhD, Jorge Oksenberg PhD, Heinz Wiendl MD, Klaus Berger PhD, Marco Hermesdorf PhD, Fredrik Piehl MD, David Conen MD, Andreas Buser MD, Ludwig Kappos MD, Michael Khalil MD, PhD, Cristina Granziera MD, PhD, Ahmed Abdelhak MD, David Leppert MD, Eline A.J. Willemse PhD, Jens Kuhle MD, PhD, for the Swiss MS Cohort study (SMSC)\",\"doi\":\"10.1002/ana.27096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Elevated sGFAP levels (Z score >1) at 1 year were associated with a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17–2.78]; <i>p</i> = 0.0079) than elevated sNfL levels (HR, 1.45 [0.95–2.24], <i>p</i> = 0.0886) in a combined model. Independent of PIRA events, sGFAP levels longitudinally increased by 0.49 Z score units per 10 years follow-up (estimate, 0.49 [0.29, 0.69], <i>p</i> < 0.0001). In patients experiencing PIRA, sGFAP Z scores were 0.52 Z score units higher versus stable patients (0.52 [0.22, 0.83], <i>p</i> = 0.0009). Different sNfL Z score trajectories were found in pwMS with versus without PIRA (interaction <i>p</i> = 0.0028), with an average decrease of 0.92 Z score units per 10 years observed without PIRA (−0.92 [−1.23, −0.60], <i>p</i> < 0.0001), whereas levels in patients with PIRA remained high.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>Elevated sGFAP and lack of drop in sNfL after BCDT start are associated with increased risk of future PIRA. These findings provide a rationale for combined monitoring of sNfL and sGFAP in pwMS starting BCDT to predict the risk of PIRA, and to use sGFAP as an outcome in clinical trials aiming to impact on MS progressive disease biology. ANN NEUROL 2025;97:104–115</p>\\n </section>\\n </div>\",\"PeriodicalId\":127,\"journal\":{\"name\":\"Annals of Neurology\",\"volume\":\"97 1\",\"pages\":\"104-115\"},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683165/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ana.27096\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ana.27096","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis
Objective
To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.
Methods
A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.
Results
Elevated sGFAP levels (Z score >1) at 1 year were associated with a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17–2.78]; p = 0.0079) than elevated sNfL levels (HR, 1.45 [0.95–2.24], p = 0.0886) in a combined model. Independent of PIRA events, sGFAP levels longitudinally increased by 0.49 Z score units per 10 years follow-up (estimate, 0.49 [0.29, 0.69], p < 0.0001). In patients experiencing PIRA, sGFAP Z scores were 0.52 Z score units higher versus stable patients (0.52 [0.22, 0.83], p = 0.0009). Different sNfL Z score trajectories were found in pwMS with versus without PIRA (interaction p = 0.0028), with an average decrease of 0.92 Z score units per 10 years observed without PIRA (−0.92 [−1.23, −0.60], p < 0.0001), whereas levels in patients with PIRA remained high.
Interpretation
Elevated sGFAP and lack of drop in sNfL after BCDT start are associated with increased risk of future PIRA. These findings provide a rationale for combined monitoring of sNfL and sGFAP in pwMS starting BCDT to predict the risk of PIRA, and to use sGFAP as an outcome in clinical trials aiming to impact on MS progressive disease biology. ANN NEUROL 2025;97:104–115
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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