Simple blood test may help guide personalized NMOSD treatment
Study identifies three proteins that could help track relapses and recovery
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A simple blood test measuring the levels of three proteins linked to brain damage and inflammation may help guide management of neuromyelitis optica spectrum disorder (NMOSD) related to antibodies against the AQP4 protein, a study suggests.
People with NMOSD who were experiencing a disease relapse, when symptoms worsen, had elevated levels of two proteins in their bloodstream, while another protein was higher during disease remission, the time between relapses with stable or no symptoms.
The “combined detection of these biomarkers provides a potential non-invasive approach for personalized NMOSD management,” researchers wrote, calling for future studies to “validate these findings and establish clinical thresholds.”
The study, “Serum brain injury biomarkers in patients with NMOSD: dynamic changes and clinical significance,” was published in the European Journal of Medical Research.
Study compares blood biomarkers related to brain injury
NMOSD is caused by immune attacks that lead to inflammation and damage in the spinal cord and the optic nerves that carry visual signals between the eyes and the brain. Most patients carry self-reactive antibodies against AQP4, a protein found on support cells in the brain and spinal cord called astrocytes.
The disease typically follows a relapsing-remitting course, in which relapses, also known as attacks, are followed by periods of remission. Each relapse can lead to irreversible nerve damage and progressively worsening disability over time.
However, previous research has not systematically compared blood biomarkers related to brain injury between attack and remission phases in people with AQP4-related NMOSD, nor compared these findings with clinical data.
With this in mind, a team of researchers in China analyzed data from 69 AQP4-related NMOSD patients (88.4% female), of whom 32 (27 females) had experienced a relapse within 60 days of blood sampling.
Relapses were defined as the onset of new or worsening symptoms, along with worsening overall disability, as indicated by at least a one-point score increase (worsening) in the validated Expanded Disability Status Scale (EDSS).
The remaining 37 (34 females) were in remission, defined as an attack more than 60 days before blood sampling, stable or improved symptoms for at least one month, and reduced overall disability since the attack, as indicated by a 0.5-point or higher EDSS score drop. All were receiving immunosuppressive treatments at the time of blood sampling.
Elevated blood NfL levels associated with worse disability
Comparisons showed no differences in age, sex, or relapse frequency between the two groups. But those in remission had been living with NMOSD for significantly longer, whereas the recent attack group had significantly worse disability (higher EDSS scores).
Blood samples were tested for four biomarkers associated with brain injury. Two of them, neurofilament light chain (NfL) and neurofilament heavy chain (NfH), reflect nerve damage. The other two, monocyte chemoattractant protein 1 (MCP-1) and matrix metalloproteinase 9 (MMP-9), indicate inflammation, tissue remodeling, and immune cell activity.
Results showed that median NfL levels were significantly higher, by 70.9%, in NMOSD patients in the attack phase than in those in remission. Similarly, median MMP-9 levels were significantly higher, by 30.8%, in the recent attack group.
NfH levels were also higher among patients who had experienced a recent relapse relative to those in remission, but the difference was not statistically significant, meaning it could have occurred by chance.
In contrast, median MCP-1 levels were significantly higher, by 83.5%, in the remission group compared with the relapse group, a result that challenges the traditional view of MCP-1 as a pro-inflammatory signaling protein, the team noted.
The combined elevation of NfL and MMP-9, concurrent with decreased MCP-1, could potentially help identify patients with more active disease.
Further analyses showed that elevated blood NfL levels were significantly associated with worse disability (higher EDSS scores), higher anti-AQP4 antibody levels, and a shorter disease duration.
Notably, elevated blood NfL also strongly correlated with a shorter window between the last attack and blood sampling, suggesting that “NfL may have potential for monitoring treatment response,” the researchers wrote.
Similar to NfL, NfH levels also followed anti-AQP4 antibody levels. While MMP-9 showed no significant association with any clinical assessment, MCP-1, which was higher during remission, was significantly linked to a longer time since the last attack.
Between biomarkers, NfL and NfH levels paralleled each other, while high MCP-1 correlated with low MMP-9.
“The combined elevation of NfL and MMP-9, concurrent with decreased MCP-1, could potentially help identify patients with more active disease,” the researchers wrote. Still, “specific quantitative thresholds and clinical utility must be confirmed in large-scale prospective studies before implementation in routine clinical practice.”
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