SERUM NEUROFILAMENT LIGHT AND GFAP ARE ASSOCIATED WITH DISEASE SEVERITY IN INFLAMMATORY DISORDERS WITH AQUAPORIN-4 OR MYELIN OLIGODENDROCYTE GLYCOPROTEIN ANTIBODIES

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are inflammatory autoimmune disorders of the central nervous system (CNS) characterized by severe relapses and cumulative neurological disabilities. Most NMOSD patients possess antibodies against aquaporin-4 (AQP4-ab), while MOGAD is associated with antibodies against myelin oligodendrocyte glycoprotein (MOG-ab). This study aims to evaluate serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (GFP) as potential biomarkers for disease severity in NMOSD with AQP4-ab or MOGAD.

Key Findings: The study enrolled 51 AQP4-ab-positive NMOSD patients, 42 MOGAD patients, and 31 relapsing-remitting multiple sclerosis (RRMS) patients, along with 28 healthy controls (HCs). sNfL and sGFAP levels were measured using ultrasensitive single-molecule array (SIMOA) assays. The results revealed that sNfL levels were significantly higher in patients with AQP4-ab-positive NMOSD, MOGAD, and RRMS than HCs. Additionally, GFP levels were remarkably increased in AQP4-ab-positive NMOSD and MOGAD patients compared to HCs. The GFP/sNfL ratio demonstrated good discrimination among the disease groups, indicating distinct pathogenesis. Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale (EDSS) scores in AQP4-ab-positive NMOSD and MOGAD patients.

Innovative Tools: The researchers employed ultrasensitive SIMOA assays to measure sNfL and sGFAP levels, providing high sensitivity and precision. This advanced technology allowed for the accurate quantification of these biomarkers in serum samples, facilitating the assessment of their potential as indicators of disease severity and activity in NMOSD and MOGAD.

Behavioral Assessments: Although the study did not include behavioral assessments, the clinical implications of increased sNfL and sGFAP levels are significant. Elevated sNfL indicates neuronal-axonal injury, while increased sGFAP reflects astrocytic damage. These biomarkers can be used to monitor disease progression and the effectiveness of therapeutic interventions, ultimately impacting patient care and outcomes.

Biochemical Analysis: The study found that sNfL levels were significantly elevated in AQP4-ab-positive NMOSD, MOGAD, and RRMS patients compared to HCs, with MOGAD and RRMS patients showing higher levels than AQP4-ab-positive NMOSD patients. sGFAP levels were also significantly higher in AQP4-ab-positive NMOSD and MOGAD patients compared to HCs and RRMS patients. The GFP/sNfL ratio effectively discriminated between the disease groups, reflecting different pathological processes. Both biomarkers were associated with EDSS scores, indicating their potential as measures of disease severity.

Conclusions: This study proves that sNfL and sGFAP levels are associated with disease severity in AQP4-ab-positive NMOSD and MOGAD patients. The GFP/sNfL ratio offers additional insight into the distinct pathophysiological mechanisms underlying these disorders. These findings suggest that sNfL and sGFAP could be valuable biomarkers for monitoring disease activity and guiding treatment strategies. Future research should validate these results in larger cohorts and explore the long-term utility of these biomarkers in clinical practice.

Join the Discussion: We invite you to share your thoughts on the potential of sNfL and sGFAP biomarkers for NMOSD and MOGAD. How might these biomarkers influence the management and treatment of patients with these conditions? What additional research is needed to understand their role in disease pathology further? Join the conversation in the comments below and share your insights and ideas.

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Original Research: The original research, "Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies," is available on PubMed here.