Biomarker Assessment in Neuromyelitis Optica Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSD) constitute a group of rare, relapse-prone autoimmune conditions of the central nervous system characterised by demyelination and astrocytopathy. The discovery of aquaporin-4 immunoglobulin G (AQP4-IgG) transformed diagnostic criteria, yet up to a fifth of patients remain seronegative, spurring the search for complementary biomarkers. Fluid-based markers such as glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) quantify astrocyte and axonal injury, respectively, and correlate with disease activity, severity and recovery. Advances in high-sensitivity immunoassays, notably single-molecule array technology, permit detection of these proteins at subfemtomolar concentrations in blood and cerebrospinal fluid. Emerging approaches include metabolomic profiling of aromatic amino acids, cytokine and complement panels, and proteomic algorithms integrating GFAP, NfL and tau to refine diagnostic subtypes and predict relapse risk. A multi-modal biomarker strategy holds promise for early diagnosis, tailored therapy and objective monitoring of treatment response in NMOSD.

Research from Nature Portfolio

A recent prospective study evaluated serum neurofilament light chain, glial fibrillary acidic protein and brain-derived neurotrophic factor in patients with recent optic neuritis, including those with AQP4-IgG, MOG-IgG and double-seronegative status. Serum GFAP levels were markedly higher during acute attacks and closely tracked visual acuity, while BDNF concentrations at baseline correlated with recovery over follow-up. These findings demonstrate the clinical utility of highly sensitive immunoassays in quantifying circulating markers of astrocytic damage and neuronal repair, underlining their potential as disease activity and prognostic biomarkers in NMOSD-related optic neuritis.

Biomarker Assessment in Neuromyelitis Optica Spectrum Disorders publication trend

The graph below shows the total number of articles in biomarker assessment in neuromyelitis optica spectrum disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Aquaporin-4 immunoglobulin G (AQP4-IgG): Autoantibody targeting the astrocytic water channel aquaporin-4, defining most NMOSD cases.

Glial fibrillary acidic protein (GFAP): Astrocytic intermediate filament protein released into body fluids upon astrocyte injury.

Neurofilament light chain (NfL): Axonal cytoskeletal protein released following neuroaxonal damage.

Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG): Autoantibody against oligodendrocyte myelin protein, marking a distinct demyelinating disorder.

Single-molecule array (Simoa): Ultra-sensitive immunoassay platform enabling quantification of protein biomarkers at femtomolar levels.

References

1. Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies. Frontiers in Immunology (2021).
2. Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Journal of Neuroinflammation (2021).
3. Profile and potential role of novel metabolite biomarkers, especially indoleacrylic acid, in pathogenesis of neuromyelitis optica spectrum disorders. Frontiers in Pharmacology (2023).
4. Serum proteins for monitoring and predicting visual function in patients with recent optic neuritis. Scientific Reports (2023).
5. Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: a mini review. Frontiers in Neurology (2024).
6. The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies. Clinical Proteomics (2024).