Factors found to affect NfL levels, a biomarker used in MS research
NfL levels influenced by age, BMI, blood storage conditions: Study
Blood levels of neurofilament light chain (NfL) — a biomarker of nerve cell damage used in multiple sclerosis (MS) research — are influenced by factors such as age, body mass index (BMI), and storage conditions of the blood samples, according to a recent report.
Such factors may need to be considered and adjusted for in studies where NfL is an outcome measure, according to researchers.
A method of adjusting NfL values for age appeared to be effective for distinguishing healthy people from MS patients, and MS patients with active inflammatory brain lesions from those without them.
The study, “Neurofilament light in serum: reference values and effect of risk factors for multiple sclerosis,” was published in Multiple Sclerosis and Related Disorders.
NfL is a structural protein in nerve cells that gets released into the surrounding space when those cells are damaged, which makes it a good biomarker of nervous system damage and neurodegeneration.
NfL levels increase with MS disease activity
The protein is elevated in the blood and cerebrospinal fluid, or the fluid surrounding the brain and spinal cord, of people with various neurodegenerative diseases, including MS. Also, NfL levels increase when MS disease activity is higher and decrease with successful treatment.
Because of this relationship, NfL is sometimes used as an outcome measure in clinical trials, with the general idea being that if a treatment lowers NfL levels, it is likely to have a positive influence on the clinical course of disease.
However, previous studies have identified various factors that can influence NfL levels in healthy people, including age, BMI, and blood volume, or the amount of fluid circulating in the blood vessels. Thus, it’s important to understand these factors, as they may have to be accounted for in studies where NfL is an outcome measure. Otherwise, they could confound, or confuse, the interpretation of the findings.
In the recent report, scientists investigated the relationship between these previously established confounding factors and NfL blood levels among more than 1,000 people without MS across four different studies.
Results generally showed, as observed in previous studies, blood NfL levels increased with age, but decreased as BMI and blood volume rose.
Moreover, storage conditions of the blood samples appeared to influence NfL levels, where storage at a warmer temperature (minus 20 C instead of minus 80 C) and for a longer period of time (more than five years) were each associated with about 20% lower blood NfL values.
The researchers noted these findings may “have substantial implications for the use of biobank samples for NFL research.”
The scientists also looked at whether certain known MS risk factors, namely smoking status and genetic variants in the HLA genes, affected NfL levels in the healthy people, but no significant relationships were observed.
NfL found elevated in 51% of newly diagnosed relapsing-remitting MS patients
NfL levels were then measured in blood samples from 72 newly diagnosed relapsing-remitting MS patients. Results showed that, compared to a Danish reference population, more than half (51.4%) of patients had elevated NfL, whereas two of the 111 healthy samples had higher levels.
Finally, the team looked for sensitive ways of using NfL values to distinguish between MS patients and healthy people, taking into account some of the factors that influence NfL levels.
They found that a simple method accounting for the effect of age seemed to perform well for distinguishing MS patients from healthy people, doing just as well as a different strategy that accounted for both age and BMI. It could also be used to distinguish MS patients with active inflammatory brain lesions from those without them.
“For the use in clinical practice, we suggest that for most patients with MS it may be sufficient to correct for the effect of age when interpreting serum [blood] concentrations of NFL,” the researchers wrote. They noted, however, that BMI and other confounders should be considered.
“This may be especially important in older patients where the presence of other neurodegenerative or vascular diseases may also result in high serum concentrations of NFL,” the team concluded.
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