Optimal timing ID’d for measuring blood biomarkers in NMOSD
Analysis of cell damage markers best done at specific times for accuracy
Blood levels of markers of brain cell damage may be used to distinguish between attack and remission periods in neuromyelitis optica spectrum disorder (NMOSD) patients, but analysis of these blood biomarkers should be done at specific times to get the best accuracy.
Those are the findings from a study by an international team of researchers that sought to “enhance clinical utility” in testing in people with NMOSD.
According to the team, “optimizing … timing … could improve accuracy in assessing NMOSD disease activity,” helping to “[support] these biomarkers’ effectiveness in distinguishing NMOSD attacks from remission.”
The study, “Blood-Based Biomarkers for Identifying Disease Activity in AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder,” was published in the journal JAMA Neurology.
Investigating NfL, GFAP levels in blood as biomarkers of disease activity
NMOSD is an inflammatory disorder that causes damage in the brain and spinal cord. Most cases are associated with the production of self-reactive antibodies against AQP4 — a protein in astrocytes, which are a class of star-shaped brain cells that provide support to neurons, or nerve cells.
The disease affects astrocytes as well as neurons, and causes symptoms such as muscle weakness and vision problems. NMOSD is characterized by attacks in which symptoms suddenly get worse interspaced by periods of disease remission.
Neurofilament light chain, called NfL, is a well-established marker of damage to neurons, while glial fibrillary acidic protein, or GFAP, is a marker of astrocyte damage. These markers can be detected in blood, and studies have suggested that these two proteins may serve as biomarkers of disability and of disability worsening during attacks in NMOSD.
“Additionally, there is debate about whether biomarkers increase during remission and whether such an increase indicates ongoing disease activity,” the researchers wrote.
Studies to date have reported inconsistent results, which “may arise from variations in the timing of attack and remission assessments, often arbitrarily set at 2 or 3 months postattack, without considering the temporal dynamics of the biomarkers,” the researchers wrote.
With this in mind, the team now set out to determine the most appropriate timing for assessing attack and remission phases in NMOSD patients based on blood levels of NfL and GFAP.
The researchers retrospectively analyzed 202 blood samples from 74 people with NMOSD that were collected at different points in time up to six months after an attack. These samples were collected from February 2008 to October 2023.
Nearly all of the patients (96%) were women, and their median age at the time of blood collection was 35. Blood occurred a median of five years after disease onset. Most patients (86%) were on immunosuppressive treatments used off-label for NMOSD; none were on NMOSD-approved therapies.
Overall accuracy higher than 90% for differentiating remission, attack phases
The data showed that, after an attack, blood levels of GFAP rapidly rise, reaching a peak about a week after attack symptoms become apparent. By contrast, blood NfL levels increase more slowly, peaking at about five weeks after symptoms appear.
Based on these data, the researchers determined that GFAP should be measured within the first week after an attack for optimum accuracy, whereas NfL should be measured between one and eight weeks after an attack.
To validate these findings, the researchers analyzed blood samples from two independent groups of NMOSD patients. One, from Germany, comprised 34 patients, while the other, from Brazil, involved 69 patients.
Using cutoff NfL and GFAP values that were identified in the previous analysis, as well as their specific timeframes for analysis, the researchers were able to discriminate between patients experiencing attacks and those in disease remission with overall accuracy greater than 90%. The accuracy was 94% for NfL and 100% for GFAP, per the researchers.
By refining their predictive accuracy and enhancing their reliability, our research contributes to improving the use of these biomarkers in clinical settings, facilitating more informed and precise management of patients with NMOSD.
Importantly, the team noted, blood GFAP levels were able to correctly identify all patients in an attack phase and all of those in a remission phase.
As such, blood GFAP levels “may help differentiate genuine attacks from pseudoattacks,” while NfL’s association “with neuronal damage severity in NMOSD attacks offers insights into predicting recovery after an attack,” the team wrote.
According to the team, “this study significantly advances our comprehension of [blood NfL and GFAP levels] as biomarkers for NMOSD,” and shows “optimal timing and thresholds” for testing.
“By refining their predictive accuracy and enhancing their reliability, our research contributes to improving the use of these biomarkers in clinical settings, facilitating more informed and precise management of patients with NMOSD,” the researchers concluded.
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