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Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis.
Meier, Stephanie; Willemse, Eline A J; Schaedelin, Sabine; Oechtering, Johanna; Lorscheider, Johannes; Melie-Garcia, Lester; Cagol, Alessandro; Barakovic, Muhamed; Galbusera, Riccardo; Subramaniam, Suvitha; Barro, Christian; Abdelhak, Ahmed; Thebault, Simon; Achtnichts, Lutz; Lalive, Patrice; Müller, Stefanie; Pot, Caroline; Salmen, Anke; Disanto, Giulio; Zecca, Chiara; D'Souza, Marcus; Orleth, Annette; Khalil, Michael; Buchmann, Arabella; Du Pasquier, Renaud; Yaldizli, Özgür; Derfuss, Tobias; Berger, Klaus; Hermesdorf, Marco; Wiendl, Heinz; Piehl, Fredrik; Battaglini, Marco; Fischer, Urs; Kappos, Ludwig; Gobbi, Claudio; Granziera, Cristina; Bridel, Claire; Leppert, David; Maleska Maceski, Aleksandra; Benkert, Pascal; Kuhle, Jens.
Afiliação
  • Meier S; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Willemse EAJ; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Schaedelin S; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Oechtering J; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Lorscheider J; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Melie-Garcia L; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Cagol A; Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Barakovic M; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Galbusera R; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Subramaniam S; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Barro C; Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Abdelhak A; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Thebault S; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Achtnichts L; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Lalive P; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Müller S; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Pot C; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Salmen A; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Disanto G; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Zecca C; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • D'Souza M; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Orleth A; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Khalil M; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Buchmann A; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Du Pasquier R; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Yaldizli Ö; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Derfuss T; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Berger K; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Hermesdorf M; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Wiendl H; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Piehl F; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Battaglini M; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Fischer U; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Kappos L; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
  • Gobbi C; Multiple Sclerosis Centre, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
  • Granziera C; Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Switzerland.
  • Bridel C; Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Leppert D; Department of Neurology, Harvard Medical School, Boston, Massachusetts.
  • Maleska Maceski A; Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco.
  • Benkert P; Department of Medicine and the Ottawa Hospital Research Institute, The University of Ottawa, Ottawa, Ontario, Canada.
  • Kuhle J; Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
JAMA Neurol ; 80(3): 287-297, 2023 03 01.
Article em En | MEDLINE | ID: mdl-36745446
ABSTRACT
Importance There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS).

Objective:

To determine how serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression. Design, Setting, and

Participants:

Data were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022. The SMSC is a prospective, multicenter study performed in 8 centers in Switzerland. For this nested study, participants had to meet the following inclusion criteria cohort 1, patients with MS and either stable or worsening disability and similar baseline Expanded Disability Status Scale scores with no relapses during the entire follow-up; and cohort 2, all SMSC study patients who had initiated and continued B-cell-depleting treatment (ie, ocrelizumab or rituximab). Exposures Patients received standard immunotherapies or were untreated. Main Outcomes and

Measures:

In cohort 1, sGFAP and sNfL levels were measured longitudinally using Simoa assays. Healthy control samples served as the reference. In cohort 2, sGFAP and sNfL levels were determined cross-sectionally.

Results:

This study included a total of 355 patients (103 [29.0%] in cohort 1 median [IQR] age, 42.1 [33.2-47.6] years; 73 female patients [70.9%]; and 252 [71.0%] in cohort 2 median [IQR] age, 44.3 [33.3-54.7] years; 156 female patients [61.9%]) and 259 healthy controls with a median [IQR] age of 44.3 [36.3-52.3] years and 177 female individuals (68.3%). sGFAP levels in controls increased as a function of age (1.5% per year; P < .001), were inversely correlated with BMI (-1.1% per BMI unit; P = .01), and were 14.9% higher in women than in men (P = .004). In cohort 1, patients with worsening progressive MS showed 50.9% higher sGFAP levels compared with those with stable MS after additional sNfL adjustment, whereas the 25% increase of sNfL disappeared after additional sGFAP adjustment. Higher sGFAP at baseline was associated with accelerated gray matter brain volume loss (per doubling 0.24% per year; P < .001) but not white matter loss. sGFAP levels remained unchanged during disease exacerbations vs remission phases. In cohort 2, median (IQR) sGFAP z scores were higher in patients developing future confirmed disability worsening compared with those with stable disability (1.94 [0.36-2.23] vs 0.71 [-0.13 to 1.73]; P = .002); this was not significant for sNfL. However, the combined elevation of z scores of both biomarkers resulted in a 4- to 5-fold increased risk of confirmed disability worsening (hazard ratio [HR], 4.09; 95% CI, 2.04-8.18; P < .001) and PIRA (HR, 4.71; 95% CI, 2.05-9.77; P < .001). Conclusions and Relevance Results of this cohort study suggest that sGFAP is a prognostic biomarker for future PIRA and revealed its complementary potential next to sNfL. sGFAP may serve as a useful biomarker for disease progression in MS in individual patient management and drug development.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Idioma: En Ano de publicação: 2023 Tipo de documento: Article