Can Certain Proteins Be Linked to Disease Severity in Multiple Sclerosis?

A recent study investigated neuronal and astroglial markers in patients with multiple sclerosis (MS) and aquaporin‐4 antibody‐seropositive neuromyelitis optica spectrum disorders (NMOSD) to compare the clinical implications of these serum markers according to patient age.

The researchers said it is the first such study to examine this issue and that their results confirm the use of these proteins as biomarkers in demyelinating diseases of the central nervous system (CNS).

Serum neurofilament light protein (NfL) and glial fibrillary acidic protein (GFAP) are cytoskeletal scaffolding proteins in neurons and astrocytes, respectively. Both can be measured from bodily fluids, including cerebral spinal fluid (CSF) and blood, leading some to think they can be used as biomarker ins CNS demyelinating diseases. The proteins can be measured by ultrasensitive single‐molecule array (Simoa) technology.

However, aging processes may affect these proteins, altering their ability to be used as a disease biomarker.

In this study, consecutive patients with MS and NMOSD from a neurology department in the Republic of Korea were prospectively recruited between July 2018 and February 2019. All patients underwent Simoa analysis; in addition, patients fulfilled the 2017 McDonald criteria for MS and the 2015 Wingerchuk criteria for NMOSD.

Through Simoa, researchers measured NfL and GFAP from 117 patients with MS and 63 patients with NMOSD. The authors correlated between the markers and disease severity according to the Expanded Disability Status Scale (EDSS) scores and by 3 age groups (≤44, 45—54, and ≥55 years).

The degrees of correlation between the disease (or age) groups were compared using Fisher’s z‐transformation of correlation coefficients. When correlations between the age groups were compared, the youngest group was referenced; a Bonferroni correction corrected multiple comparisons.

Patient median age was 47 years and the majority were female. Patients with NMOSD were older than patients with MS and had more frequent relapses and recent attacks and a higher EDSS score.

By age, both NfL and GFAP levels tended to increase with EDSS scores in all age groups for patients with MS. The degrees of these correlations between serum markers and EDSS scores did not differ significantly among the age groups.

However, in patients with NMOSD, correlations between serum markers and EDSS scores were significantly different by age; in particular, GFAP levels showed significantly stronger positive correlations with EDSS scores in the youngest age group, but not the oldest age group (Pearson r, ≤ 44 years vs. ≥ 55 years, 0.754 vs. 0.075, P = .044 [corrected, Bonferroni]).

NfL levels showed the opposite direction, where the strongest positive associations with EDSS scores were seen in the oldest age group (Pearson r, ≤44 years vs. ≥55 years, —0.182 vs. 0.594, P = .068 [corrected, Bonferroni]).

The differences between serum NfL and GFAP levels in patients with MS and NMOSD show that only the age of the patient in NMOSD and disease severity is related. Disease severity in MS is not reflected by these proteins when factoring in age.

This indicates that the pathological processes and progression of the 2 diseases differ and that these serum biomarker levels may need to be interpreted by patient age and disease type in order to come up with different clinical strategies, the authors said.

Reference

Lee EJ, Lim YM, Kim S, et al. Clinical implication of serum biomarkers and patient age in inflammatory demyelinating diseases. Ann Clin Transl Neurol. Published online June 4, 2020. doi:10.1002/acn3.51070