Neurology(R) neuroimmunology & neuroinflammation · 2026
Serum Glial Fibrillary Acidic Protein and Retinal Neuronal Loss as Additive Prognostic Markers of Disability in Multiple Sclerosis.
СтатьяНазвание и аннотация: Перевод в очереди
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Sellathurai Shaumiya, Schoenholzer Kean, Burguet Villena Federico, Cerdá-Fuertes Nuria, Hofer Lisa, Schaedelin Sabine Anna, Kana Veronika, Mahenthiran Pradesta, D'Souza Marcus, Maleska Maceski Aleksandra, Derfuss Tobias J, Oechtering Johanna, Gugleta Konstantin, Kappos Ludwig, Petzold Axel, Granziera Cristina, Benkert Pascal, Kuhle Jens, Papadopoulou Athina
Аннотация
BACKGROUND AND OBJECTIVES: In people with multiple sclerosis (pwMS), optical coherence tomography (OCT) quantifies loss of neurons (macular ganglion cell-inner plexiform layer [mGCIPL]) and axons (peripapillary retinal nerve fiber layer [pRNFL]) in the retina. Serum glial fibrillary acidic protein (sGFAP) is a promising astrocytic biomarker to capture disease progression in pwMS. We aimed to investigate the relationship between OCT markers and sGFAP in pwMS and explore their additive value in predicting disability progression.
METHODS: PwMS and healthy controls underwent OCT at baseline (BL), excluding eyes with inter-eye asymmetry. Age, sex, and body mass index-adjusted Z scores of sGFAP were calculated. Cross-sectional and longitudinal associations between sGFAP and retinal layers were estimated using linear regression- and mixed-effects models (LMM). The additive effect of BL-OCT and BL-sGFAP on the trajectory of the Expanded Disability Status Scale (EDSS) was estimated using LMM, whereby pwMS were stratified into: group (1): low sGFAP Z score (<3rd quartile, <Q3) and thick mGCIPL (>Q1); group (2): high sGFAP Z score (≥Q3) and thick mGCIPL or low sGFAP Z Score and thin mGCIPL (≤Q1); and group (3): high sGFAP and thin mGCIPL.
RESULTS: Two hundred and sixty-one pwMS (mean age: 48 years (y), female: 63%, on disease-modifying treatment: 80%, mean thickness of pRNFL: 94 μm and mGCIPL: 66 μm) and 52 controls (age: 52 years, female: 65%, pRNFL: 101 μm, mGCIPL: 72 μm) were included. At BL, pRNFL (β = -0.01, p = 0.042) and mGCIPL (β = -0.02, p = 0.013) were negatively associated with sGFAP Z scores in pwMS, but not in controls (p = 0.950, p = 0.386). BL-mGCIPL was also associated with sGFAP trajectories (β = -0.003, p = 0.044), over a median follow-up of 2.9 years. Compared with pwMS with good results in both markers (group 1), those with either high sGFAP or thin mGCIPL had a steeper EDSS increase (β = 0.030, p = 0.048), while pwMS with both high sGFAP and thin mGCIPL (group 3) showed the steepest trajectory of the EDSS (β = 0.101, p < 0.001).
DISCUSSION: Our findings show a close relationship between astrocytic activation/injury and neurodegeneration in the CNS, measured at the retinal level. Moreover, they highlight an additive role of mGCIPL and sGFAP for identification of pwMS at higher risk of disability worsening.
METHODS: PwMS and healthy controls underwent OCT at baseline (BL), excluding eyes with inter-eye asymmetry. Age, sex, and body mass index-adjusted Z scores of sGFAP were calculated. Cross-sectional and longitudinal associations between sGFAP and retinal layers were estimated using linear regression- and mixed-effects models (LMM). The additive effect of BL-OCT and BL-sGFAP on the trajectory of the Expanded Disability Status Scale (EDSS) was estimated using LMM, whereby pwMS were stratified into: group (1): low sGFAP Z score (<3rd quartile, <Q3) and thick mGCIPL (>Q1); group (2): high sGFAP Z score (≥Q3) and thick mGCIPL or low sGFAP Z Score and thin mGCIPL (≤Q1); and group (3): high sGFAP and thin mGCIPL.
RESULTS: Two hundred and sixty-one pwMS (mean age: 48 years (y), female: 63%, on disease-modifying treatment: 80%, mean thickness of pRNFL: 94 μm and mGCIPL: 66 μm) and 52 controls (age: 52 years, female: 65%, pRNFL: 101 μm, mGCIPL: 72 μm) were included. At BL, pRNFL (β = -0.01, p = 0.042) and mGCIPL (β = -0.02, p = 0.013) were negatively associated with sGFAP Z scores in pwMS, but not in controls (p = 0.950, p = 0.386). BL-mGCIPL was also associated with sGFAP trajectories (β = -0.003, p = 0.044), over a median follow-up of 2.9 years. Compared with pwMS with good results in both markers (group 1), those with either high sGFAP or thin mGCIPL had a steeper EDSS increase (β = 0.030, p = 0.048), while pwMS with both high sGFAP and thin mGCIPL (group 3) showed the steepest trajectory of the EDSS (β = 0.101, p < 0.001).
DISCUSSION: Our findings show a close relationship between astrocytic activation/injury and neurodegeneration in the CNS, measured at the retinal level. Moreover, they highlight an additive role of mGCIPL and sGFAP for identification of pwMS at higher risk of disability worsening.