New biomarker may help gauge disease severity in NMOSD
Higher spinal fluid CHIT1 levels were linked to more active disease
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People with neuromyelitis optica spectrum disorder (NMOSD) have significantly higher levels of chitotriosidase-1 (CHIT1), a protein involved in immune and inflammatory responses, in their cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord, a study shows.
CSF CHIT1 levels were also significantly associated with NMOSD activity and severity. Higher levels were found in people with active inflammatory brain lesions and in those with greater disability.
The findings suggest that CSF CHIT1 levels “may serve as a potential diagnostic and prognostic marker for NMOSD,” the researchers wrote.
The study, “Elevated levels of cerebrospinal fluid CHIT1 correlate with disease activity in neuromyelitis optica spectrum disorder,” was published in Neurological Sciences.
Understanding inflammation and immune activity in NMOSD
NMOSD is characterized by inflammation in the spinal cord and the optic nerve, which relays visual signals between the eye and brain. The disease often follows a relapsing pattern, with sudden inflammatory attacks that can damage nerves and lead to long-term neurological problems.
Although the exact causes of nerve damage in NMOSD are not fully understood, self-reactive antibodies against the AQP4 protein and activation of microglia are thought to play a role. Microglia are immune cells that reside in the brain, spinal cord, and optic nerves.
These cells help coordinate immune responses, fight infections in the brain, and repair injury. However, they can also contribute to the development of demyelinating lesions in NMOSD. These lesions damage myelin, the protective coating that surrounds nerve fibers.
CHIT1, a marker of microglia activation, has shown promise as a diagnostic and prognostic biomarker in several chronic inflammatory diseases, including conditions affecting the brain and spinal cord. However, “its role in NMOSD remains unclear,” the researchers wrote.
Researchers examine CHIT1 as a potential biomarker in NMOSD
To better understand whether CHIT1 could serve as a biomarker in NMOSD, researchers at a hospital in China measured CHIT1 levels in blood and CSF from three groups: 34 people with NMOSD, 30 people with noninflammatory neurological conditions, and 30 healthy volunteers.
Across the three groups, participants had mean ages ranging from about 54 to 56, and most were women. Among those with NMOSD, the average disease duration was 1.2 years, with an annual relapse rate of 1.58. Age and sex did not differ significantly between the NMOSD group and the comparison groups.
The researchers found that CHIT1 levels in CSF were significantly higher in people with NMOSD than in those with noninflammatory neurological conditions (2.65 vs. 2.21 picograms [pg]/mL). In contrast, CHIT1 levels measured in blood did not differ significantly between the NMOSD group and either comparison group.
Additional analyses showed that CSF CHIT1 levels could distinguish people with NMOSD from those with noninflammatory neurological conditions with about 73% accuracy, supporting its potential use as a diagnostic biomarker.
Higher CSF CHIT1 levels linked to more active and severe disease
When the analysis focused only on people with NMOSD, those who had gadolinium-enhancing lesions, a sign of active inflammation on brain imaging, showed significantly higher CHIT1 levels in their spinal fluid than those without these lesions (2.81 vs. 2.41 pg/mL).
Higher CHIT1 levels in CSF were also significantly associated with greater disability, measured using the Expanded Disability Status Scale (EDSS), where higher scores indicate more severe impairment.
The researchers did not find significant links between CSF CHIT1 levels and how often relapses occurred each year, how long someone had been living with NMOSD, the length of spinal cord lesions, or CSF levels of total protein, C-reactive protein (a marker of inflammation), or immune cells.
These findings point to “a potential [disease-causing] role of CHIT1 in NMOSD,” and suggest that “measuring the [CSF] CHIT1 level may help identify patients experiencing rapid disease progression,” the researchers wrote.
The researchers cautioned that the study’s small sample size may limit how broadly the findings can be applied. They wrote that “further studies are needed to … evaluate the potential utility of the CHIT1 level for patient stratification in upcoming therapeutic trials on immune and inflammatory processes in NMOSD.”
