Serum Glial Fibrillary Acidic Protein compared with Neurofilament Light Chain as Biomarker for Multiple Sclerosis Disease Progression
Stephanie Meier1, Pascal Benkert1, Aleksandra Maleska Maceski1, Sabine Schaedelin1, Johanna Oechtering1, Lester Melie-Garcia2, Alessandro Cagol2, Muhamed Barakovic2, Riccardo Galbusera2, Lutz Achtnichts3, Patrice H. Lalive4, Claire Bridel4, Stefanie Müller5, Caroline Pot6, Anke Salmen7, Giulio Disanto8, Chiara Zecca8, Ahmed Abdelhak9, Christian Barro10, Simon Thebault11, Marcus D’Souza1, Tobias Derfuss1, Annette Orleth1, Michael Khalil12, Özguer Yaldizli1, Marco Hermesdorf13, Heinz Wiendl14, Fredrik Piehl15, Urs Fischer1, Ludwig Kappos1, Claudio Gobbi8, Cristina Granziera2, David Leppert1, Eline A.J. Willemse1, Jens Kuhle1
1Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland, 2Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering; Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland, 3Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland, 4Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology, University Hospital of Geneva and Faculty of Medicine, Geneva, Switzerland, 5Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland, 6Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, 7Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, 8Multiple Sclerosis Center (MSC), Department of Neurology, Neurocenter of Southern Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Lugano, Switzerland, 9Weill Institute for Neurosciences, Department of Neurology, University of California at San Francisco (UCSF), San Francisco, California, USA, 10Department of Neurology, Harvard Medical School, Boston, MA, USA, 11Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada, 12Department of Neurology, Medical University of Graz, Graz, Austria, 13Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany, 14Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany, 15Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Center for Neurology, Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden

To compare how serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) correlate with progression and acute inflammation in multiple sclerosis (MS).


There are insufficient diagnostic tools to anticipate ‘pure progression’ and acute inflammation in MS. 


sGFAP and sNfL were measured using Simoa assays in three cohorts of patients of the Swiss MS Cohort: 1) worsening progressive MS (wPMS; 184 samples (s)/18 patients (p), median follow-up (FU): 6.5 years (y), median EDSS baseline (BL)/last visit 4.0/6.0); 2) clinically stable MS (stMS; 169s/19p, 7.1 y, EDSS 3.0/2.5) (both relapse-free during FU); 3) Relapsing MS (132s/66p) during a) acute disease activity (relapse/contrast enhancing lesions); 66s) and b) stable phase (66s); and healthy controls (HC; 485s/259p; BL and 1y FU). Multivariable mixed models were applied to longitudinally compare log-transformed sGFAP/sNfL between groups 1) versus 2); 3a) versus 3b); and adjusted mixed/Cox regression models for the association between BL sGFAP/sNfL levels and brain volume loss (BVL) and time to confirmed disability worsening (CDW) in groups 1) and 2). 


sGFAP increased in HC with age (1.5%/y, p<0.001), decreased with body mass index (-1.1%/BMI unit, p=0.015) and was 15% higher in women than men (p=0.004). wPMS patients showed 57% higher sGFAP levels versus stMS (p=0.006) and remained 51% higher after sNfL adjustment in the model (p=0.010). In contrast, the 25% increase of sNfL in wPMS versus stMS (p=0.046) disappeared after sGFAP adjustment. Acute disease activity had no effect on sGFAP, while it increased sNfL by 53% (p<0.001). Higher sGFAP at BL was associated with accelerated gray matter BVL (per doubling (pd): 0.24%, p<0.0001), but not white matter (p=0.48). sGFAP, but not sNfL levels were associated with shorter time to CDW (HR pd: 3.63, p=0.006; HR pd: 1.90, p=0.112). 


sGFAP may be a more specific biomarker for ‘pure progression’ than sNfL.