Blood markers NfL, GFAP provide useful information in NMOSD

Patients had higher levels of NfL, GFAP than those without disease: Study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A squirting dropper is shown next to vials of blood.

Two blood markers — neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) — provide complementary clinical information about neuromyelitis optica spectrum disorder (NMOSD), a review study highlights.

“Based on the results of several studies, both NfL and GFAP are considered to have their own strengths as clinical biomarkers,” the researchers wrote.

The review study, “Neurofilament light chain as a biomarker in neuromyelitis optica spectrum disorder: a comprehensive review and integrated analysis with glial fibrillary acidic protein,” was published in Neurological Sciences.

In NMOSD, the immune system erroneously launches an inflammatory attack that damages healthy cells in the brain and spinal cord. NfL is a well-established marker of damage to nerve cells, while GFAP is a marker of damage to astrocytes — a class of star-shaped brain cells that are damaged in NMOSD.

However, “there remains a critical need for further research to assess the potential of NfL as a disease biomarker for NMOSD and its integrated role with GFAP,” the researchers wrote.

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A squirting dropper is shown next to vials of blood.

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A review of studies reporting on NfL as a potential biomarker

With this in mind, a team of scientists in Korea systematically reviewed studies published up to September 2023 reporting findings on NfL as a potential NMOSD biomarker. GFAP data were analyzed within the selected papers if analyses of GFAP levels also were performed.

A total of 13 studies were selected: 11 measured levels of these markers in the blood, while two measured them in the fluid that surrounds the brain and spinal cord.

Across the reviewed studies, results were generally consistent, showing NMOSD patients had higher levels of NfL and GFAP compared with people without neurological disorders.

However, findings of studies comparing NfL levels between NMOSD and similar neurological disorders, like multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), were inconsistent.

A few studies reported lower NfL levels in NMOSD than MS, but other studies reported opposite trends. Contradictory results also were observed for GFAP levels between NMOSD and MS patients.

Most available studies reported that people with NMOSD have higher GFAP levels than those with MS. Available data also suggested higher GFAP levels in NMOSD patients compared with MOGAD patients, but these differences failed to reach statistical significance.

“While a few studies suggested significantly lower blood levels of NfL in NMOSD patients compared to conditions such as MS and MOGAD, the ability of NfL to effectively differentiate NMOSD from other [similar] diseases remained inconclusive,” the researchers wrote. “Conversely, the results suggested some promise for GFAP as a biomarker to distinguish NMOSD from MS, although it did not consistently discriminate between NMOSD and MOGAD.”

Reports of whether NfL is increased during NMOSD attacks were also inconsistent, but six out of the seven studies that assessed GFAP as a relapse marker found significantly higher levels during attacks.

“The examination of NfL and GFAP levels between acute attacks and remission suggested that GFAP may be more useful in identifying clinical relapses,” the researchers wrote.

High NfL and GFAP levels were generally associated with greater disability, as assessed with the expanded disability status scale (EDSS), at study’s start and worsening disability during attacks.

In addition, available data suggested that blood NfL levels at the time of attack could predict disability worsening, and that these levels drop with immunosuppressive treatment.

“Both NfL and GFAP seemed to adequately reflect the EDSS score, but NfL demonstrated its advantage over GFAP in indicating attack severity during relapse and in predicting disability worsening after attacks,” the researchers wrote. “In conclusion, NfL and GFAP emerge as promising biomarkers in the NMOSD landscape, particularly in distinguishing patients from healthy individuals, assessing disease severity, and possibly reflecting treatment response.”

The scientists noted this review was limited to barely a dozen studies, stressing a need for further research into how these two markers may be used to inform care for people with NMOSD.