Summary: The blood level of the glial fibrillary acidic protein (GFAP) cellular component increases when astrocytes are damaged or activated. Elevated levels of GFAP in the blood can indicate both the current and future progression of multiple sclerosis.
Source: University of Basel
The autoimmune disease multiple sclerosis can take a variety of courses. Determining the current and future course of the disease is important in order to slow down its course as much as possible. Researchers at the University of Basel have presented a biomarker whose values in the blood allow such predictions.
The researchers focused on a cell component that is measurable in the blood and is characteristic of a certain type of brain cell. These cells, called astrocytes, play a key role in multiple sclerosis (MS) processes, which can lead for example to permanent paralysis and disability.
The blood level of this cellular component, called “glial fibrillary acidic protein” (GFAP), increases when astrocytes are activated or damaged. The new study by the research group led by Professor Jens Kuhle and published in the journal JAMA Neurology shows that elevated GFAP blood levels can indicate both current and future progression of MS. Their results are based on data from, inter alia, the Swiss Multiple Sclerosis Cohort.
Use of biomarkers is changing clinical practice
In a short space of time, the research group headed by Kuhle at the University of Basel and the University Hospital Basel has thus presented a second biomarker that can support therapy decisions in MS. Last year, the research team demonstrated that some persons with MS with an apparently stable disease course had high blood levels of the neurofilament light chain (NfL) biomarker. NfL specifically indicates neuronal damage.
These people had a significantly higher probability of presenting symptoms caused by MS in the following year. Since NfL sensitively predicts disease activity at an early stage, these patients can now be treated in a more targeted, proactive manner.
Understanding of the disease mechanism is constantly increasing
Compared with NfL, the GFAP blood marker allows conclusions to be drawn about a different aspect of the complex pathophysiology of MS. Although increased NfL blood values indicate neuronal damage, GFAP in blood specifically indicates chronic disease processes in which astrocytes are involved and that contribute to gradual progressive disability.
“GFAP and NfL thus complement each other,” says Kuhle. “They can help us in making MS therapy more individually tailored and forward-looking.” These outcomes of biomarker research bring both potential therapy monitoring and prognosis, as well as research on disease origins, a big step forward.
About this multiple sclerosis research news
Author: Barbara Peters
Source: University of Basel
Contact: Barbara Peters – University of Basel
Image: The image is in the public domain
Original Research: Closed access.
“Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis” by Stephanie Meier et al. JAMA Neurology
Abstract
Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis
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.
