Neurofilament light chain in blood, CSF may serve as MS biomarker
Study focused on whether certain proteins could potentially be used in diagnosis
Neurofilament light chain (NfL) — a protein that gets released when nerve cells are damaged — is found at high levels in the blood and cerebrospinal fluid (CSF) of people with multiple sclerosis (MS), suggesting its potential as a biomarker of the disease, a study has found. CSF is the liquid around the brain and spinal cord.
In contrast, other proteins that have been suggested as possible biomarkers of disease “may not be suitable as diagnostic and predictive markers in MS,” researchers wrote. They added that because these data come from a small number of patients, additional studies on a larger number of patients are necessary.
The study, “The role of selected NKG2DLs such as MICA, MICB and ULBP4 as potential markers in multiple sclerosis,” was published in Scientific Reports.
Neurofilament light chain levels higher in relapsing-remitting MS patients
MS is a chronic autoimmune disease in which the body’s immune system mistakenly attacks the central nervous system, particularly the myelin sheath — the protective covering around nerve fibers. This damage disrupts the normal flow of nerve signals and leads to symptoms such as muscle weakness, fatigue, vision problems, and difficulty with coordination. MS often begins with a relapsing-remitting course, where periods of worsening symptoms, or relapses, are followed by recovery.
Diagnosing MS can be difficult, especially in its early stages. There is currently no single test that can confirm the disease. Instead, doctors rely on a combination of clinical assessments, MRI scans, and lab tests, including the detection of certain proteins in the CSF that indicate inflammation in the brain or spinal cord.
In this study, the researchers explored whether certain proteins in the blood and CSF could serve as new, more accessible biomarkers for MS. The researchers focused on two main types: NKG2D ligands (MICA, MICB, and ULBP4) — proteins produced by immune cells linked to MS which may trigger or worsen inflammation — and NfL in both the blood and CSF from 20 people with relapsing-remitting MS, 23 people with early signs of damage to the brain and spinal cord, and 27 controls who did not have MS.
On average, the levels of NKG2D ligands were similar across all three groups. These proteins were therefore excluded as useful markers for diagnosing MS or predicting its onset.
In contrast, the levels of NfL were significantly higher in both the blood and CSF of people with relapsing-remitting MS. Higher levels of NfL in the blood were linked to higher levels of NfL in the CSF, suggesting that blood samples can indicate MS without the need for more invasive collection of CSF.
Researchers call for larger studies
To understand whether differences in these biomarkers could help distinguish between patients who were having a relapse or who was in a period of remission, the team measured the levels of these biomarkers in both blood and CSF of those currently experiencing a relapse and those in remission. The results showed there were no major differences between the two groups for most of the proteins.
However, the team noted that one possible reason for the lack of significant differences could be the timing of the sample collection. In most cases, the samples were not taken immediately when the relapse started. This may mean important changes in protein levels were missed.
“The results we obtained may constitute a valuable contribution to science, because they initially indicate the uselessness of soluble forms of MICA/B and ULBP4 proteins — which, based on the literature to date, seemed promising — as markers that could potentially be used in the diagnosis of patients with MS,” the researchers wrote.
The team stressed, however, that this was a pilot study with a small number of patients and that controls were not healthy individuals, but patients with other neurological diseases. As such, “further studies on a larger number of patients are therefore needed to confirm the role of the markers we selected in the [underlying disease mechanisms] of MS.”
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