Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis

Abstract

The major intermediate cytoskeletal protein of astrocytes, glial fibrillary acidic protein (GFAP), and that of axons, neurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). Patients with relapsing-remitting MS (RRMS, n = 15) or secondary progressive MS (SPMS, n = 10) and healthy control subjects (n = 28) were examined twice with an interval of 8-10 years apart. Neurological deficits were scored with the Expanded Disability Status Scale (EDSS). GFAP and NFL levels were determined in CSF by enzyme-linked immunosorbent assay (ELISA). GFAP levels and NFL levels correlated with age (r and r (s) = 0.50, p = 0.006). Adjusting for age, MS patients had increased GFAP levels compared with controls (p = 0.03) and GFAP levels correlated with neurological disability (EDSS, r = 0.51, p < 0.05) and disease progression [Multiple Sclerosis Severity Score (MSSS), r = 0.47, p < 0.05]. The mean annual increase of GFAP was 6.5 ng/L for controls, 8.1 ng/L for RRMS patients, and 18.9 ng/L for SPMS patients. GFAP level at the first examination had predictive value for neurological disability 8-10 years later (EDSS, r = 0.45, p < 0.05) but not for EDSS increase between the examinations. NFL levels were not significantly increased in MS patients compared with controls and had no relationship to disability or progression and no prognostic value for disability development. GFAP, a marker for astrogliosis, is a potential biomarker for MS progression and may have a role in clinical trials for assessing the impact of therapies on MS progression.

Recent Advances in the Treatment of Neurological Autoimmune Disorders

“…Significant contributions are being made for the disease diagnostics and management with the introduction of potential biomarkers. There are findings of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NFL) (the cytoskeletal proteins of astrocytes and axons respectively) release into the CSF during the disease progression (Axelsson et al, 2010). As per clinical data, the plasma levels of osteopontin was increased well before the induction of lesions with gadolinium (Gd) and similar profiles were observed with 7KC and 15 oxy sterol derivatives of cholesterol in MS patients.…”

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“…Microglial Iba1 and astrocytic GFAP expression are usually used as markers of glial cells, though their use as markers of cellular activation has been increasingly questioned. Augmented levels of GFAP have been associated with increased neurological disease activity and, in particular, with disability [51,52]. Astrocytes respond to various neurodegenerative insults rapidly, causing vigorous astrogliosis [53], so we questioned the use of GFAP, demonstrating that 18B12 has effects on astrocytes and potentially on their activation state.…”

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“…Moreover, the expression of the proinflammmatory cytokine Interleukin (IL)17 and the anti-inflammatory cytokine IL10 by CD4 cells are also correlated, whereas no correlations were found in cerebrospinal fluid (CSF), suggesting a lack of central regulation of pro:anti-inflammatory balance in MS [39]. Finally, Axelsson et al [40] addressed the question whether CSF glial fibrillary acidic protein (GFAP) and neurofilament light protein (NFL) levels could be possible biomarkers for progression of MS. They evaluated these proteins twice, with an interval of 8-20 years.…”

“…GFAP levels at the first examination had predictive value for neurological disability 8-10 years later, but not for EDSS increase between the examinations. Conversely, CSF NFL levels were not significantly increased in MS patients compared with controls and had no prognostic value for disability development [40].…”