GFAP in early multiple sclerosis: A biomarker for inflammation

Kassubek, Rebecca; Gorges, Martin; Schocke, Michael; Hagenston, Viktoria A.M.; Huss, André; Ludolph, Albert C.; Kassubek, Jan; Tumani, Hayrettin

doi:10.1016/j.neulet.2017.07.050

Cited by 51 publications

(41 citation statements)

References 24 publications

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“…Storoni et al 22 testified an increase in the serum levels of GFAP from 3.2 pg/mL in patients with inactive MS during remission to 5 pg/mL and relapse to the active form of the disease. Similar findings were found by Kassubek et al 23 who reported GFAP levels in RRMS were significantly higher relative to the controls. A highly significant correlation was observed between GFAP levels and gadolinium enhancement intensity as a marker of an acute exacerbation of the inflammatory processes.…”

Section: Discussionsupporting

confidence: 90%

Serum Glial Fibrillary Acidic Protein: A Surrogate Marker of the Activity of Multiple Sclerosis

Sharquie

Gawwam

Abdullah

2020

MMJ

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Objective: Multiple sclerosis (MS) is a neurodegenerative disorder with various clinical types. Glial fibrillary acidic protein (GFAP) is significantly elevated in the cerebrospinal fluid (CSF) of MS patients compared with that of healthy controls. The aim of this study is to evaluate serum levels of GFAP in relation to disease activity in relapsing-remitting MS patients and to compare them with those of healthy controls. Method: This study involved 58 MS patients of relapsing-remitting MS (RRMS) type, 22 in an active stage of the disease and 36 in remission, and 50 healthy individuals as age-and sexmatched controls. Blood samples were taken from the patients at the MS Clinic of the Baghdad Teaching Hospital, and the serum levels of GFAP were determined using the enzyme-linked immunosorbent assay (ELISA) technique. Results: Mean GFAP serum levels in 22 patients presenting in the active state of the disease (6.47±3.39 ng/ml) and 36 cases in remission were (5.33±2.82 ng/ml) (p=0.074) were determined as indicated. When RRMS patients (n=58) were compared with the healthy controls (n=50, 1.89±1.21), the difference in serum levels of GFAP was statistically significant (p<0.001). The area under the curve of the serum measures of GFAP obtained through the receiver operating characteristics was 0.903, which was also statistically significant (p<0.001). Conclusion: GFAP biomarker is an indicator of disease activity in RRMS patients, and its serum level may correlate with the state of remission or exacerbation.

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Section: Discussionsupporting

confidence: 90%

Serum Glial Fibrillary Acidic Protein: A Surrogate Marker of the Activity of Multiple Sclerosis

Sharquie

Gawwam

Abdullah

2020

MMJ

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“…Astrocyte subtype A1 is a potent direct killer of the neurons and oligodendrocytes 3 . Glial fibrillary acidic protein (GFAP) is a well-established marker of astrogliosis as numerous studies described its use for MS and reported correlations with disease severity, the extent of neuroinflammation and progression 4 – 8 . Using a proteomic approach, we previously suggested the use of GFAP in subtyping progressive forms of MS 9 .…”

Section: Introductionmentioning

confidence: 99%

Serum GFAP as a biomarker for disease severity in multiple sclerosis

Abdelhak

Huss

Kassubek

et al. 2018

Sci Rep

195

149

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While neurofilament light chain (NfL) measurement in serum is a well-established marker of neuroaxonal damage in multiple sclerosis (MS), data on astroglial markers in serum are missing. In our study, glial fibrillary acid protein (GFAP) and NfL were measured in cerebrospinal fluid (CSF) and serum of MS patients and patients with other non-inflammatory neurological diseases (OND) using the Simoa technology. Clinical data like age, gender, expanded disability status scale (EDSS) and MRI findings were correlated to neurochemical markers. We included 80 MS patients: 42 relapsing-remitting MS (RRMS), 38 progressive MS (PMS), as well as 20 OND. Serum GFAP levels were higher in PMS compared to RRMS and OND (p < 0.001, p = 0.02 respectively). Serum GFAP levels correlated with disease severity in the whole MS group and PMS (Spearman-rho = 0.5, p < 0.001 in both groups). Serum GFAP correlated with serum NfL in PMS patients (Spearman-rho = 0.4, p = 0.01). Levels of serum GFAP were higher with increasing MRI-lesion count (p = 0.01). in summary, we report elevated levels of GFAP in the serum of MS patients. Since serum levels of GFAP correlate with the clinical severity scores and MRI lesion count, especially in PMS patients, it might be a suitable disease progression marker.

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“…While the dynamics and significance of serum levels of GFAP is not well understood, GFAP is considered the archetypal marker of reactive astrocytes, 26,27 which are now understood to encompass spectrum of phenotypes both deleterious and beneficial in MS 28 . One possibility is that the sustained levels of GFAP at 12 months could represent a failure of IAHSCT to control ongoing astroglial damage, either related to MS activity 17,29 or the treatment toxicity. However, this hypothesis does not fit with the clinical picture, as by 12 months, the majority of these patients remained clinically stable if not improved slightly from pre‐IHASCT disability, with no new MRI lesions and a normalization of brain atrophy rates similar to that of healthy controls 11,30 .…”

Section: Discussionmentioning

confidence: 99%

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Thebault

Lee

Bose

et al. 2020

Ann Clin Transl Neurol

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Objective: Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as 'pseudoatrophy', related to reduced inflammation. Treatment-related neurotoxicity may be contributory. We sought objective evidence of post-IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. Methods: Sera were collected from 22 MS patients pre-and post-IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single-molecule assay. Results: Pre-IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12-month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). Interpretation: There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.

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GFAP in early multiple sclerosis: A biomarker for inflammation

Cited by 51 publications

References 24 publications

Serum Glial Fibrillary Acidic Protein: A Surrogate Marker of the Activity of Multiple Sclerosis

Serum Glial Fibrillary Acidic Protein: A Surrogate Marker of the Activity of Multiple Sclerosis

Serum GFAP as a biomarker for disease severity in multiple sclerosis

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

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