Serum glial fibrillary acidic protein may be a useful prognostic marker of disease progression in multiple sclerosis

1. Patients with progressive multiple sclerosis were more likely to have elevated levels of serum glial fibrillary acidic protein (sGFAP) than those with stable disease.

2. Combined elevation of sGFAP and serum neurofilament light chain (sNfL) was associated with significantly elevated risk of disability compared to elevation of a single marker alone.

Level of Evidence Rating: 2 (Good)

Study Rundown: Multiple sclerosis (MS) is an autoimmune disorder characterized by neurologic symptoms secondary to demyelination. Previous work has demonstrated that serum neurofilament light chain (sNfL) is an accurate marker of disease progression in MS. The present study sought to determine whether serum glial fibrillary acidic protein (sGFAP) can serve as a prognostic marker in assessing disease progression in MS.

In total, 355 patients were included, with 103 in Cohort 1, 252 in Cohort 2 and 259 as healthy controls. At baseline, sGFAP levels were positively correlated with age, negatively correlated with body mass index, and tended to be higher in women than men. sGFAP levels were highest amongst individuals with progressive MS, followed by relapsing (active) MS and then relapsing (remission) MS. Both sGFAP and sNfL levels were significantly increased in worsening, progressive MS. However, sGFAP levels were not as accurate in differentiating between active vs. remissive MS as were sNfL levels.

This study by Meier et al found that serum glial fibrillary acidic protein is an accurate marker of disease progression in MS and can be additionally informative as to the status of active versus remissive disease in combination with sNfL levels. This work is helpful in describing a serum biomarker which can help to prognosticate level disability as disease progression continues; it is thought that sGFAP may reflect astrocyte-related disease progression, whereas sNfL is associated with neuronal damage. A primary limitation of this study is the inclusion of primarily White (Cohort 1) or White & Hispanic (Cohort 2) patients, which reduces the external validity of these findings. Further study should seek to assess the clinical applicability of these findings.

Click here to read this study in JAMA Neurology

Relevant reading: Serum neurofilament light in MS: the first true blood-based biomarker?

In-Depth [prospective cohort]: A cohort study was performed: cohort 1 consisted of patients with extreme phenotypes of MS, and cohort 2 were patients with MS who had begun ocrelizumab or rituximab therapy. The control group consisted of healthy individuals who had donated blood samples to the Genome-Wide Association Study of Multiple Sclerosis study; controls were excluded if they had a family history of MS or a personal history of chronic disease. Blood samples to assess levels of sGFAP and sNfL were collected within eight days of each clinic visit using standard techniques.

sGFAP levels increased 1.5% per year of age on average (p < 0.001), decreased 1.1% with each unit of body mass index (p = 0.01) and were approximately 14.9% higher in women than men (p = 0.004). sGFAP levels amongst the following groups were significantly increased compared to healthy controls (51.8pg/mL): progressive MS (103.0pg/mL, p < 0.001), relapsing (active) MS (59.1pg/mL, p <0.001) and relapsing (remission) MS (52.9pg/mL, p= 0.01). sGFAP levels and sNfL levels were significantly increased in patients with progressive, worsening MS by 57.5% and 24.8%, respectively, following multivariable adjustment. sGFAP levels were only 4.8% increased in active versus remissive MS in an adjusted model, whereas sNfL levels were 53.2% higher in active disease.

Image: PD

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