Clinical implication of serum biomarkers and patient age in inflammatory demyelinating diseases

Ann Clin Transl Neurol. 2020 Jun;7(6):992-1001. doi: 10.1002/acn3.51070. Epub 2020 Jun 4.

Abstract

Objectives: Serum synaptic proteins levels may change with age-related neurodegeneration, affecting their clinical implications as a disease biomarker. We aimed to investigate neuronal and astroglial markers in patients with multiple sclerosis (MS) and aquaporin-4 antibody-seropositive neuromyelitis optica spectrum disorders (NMOSD) to compare the clinical implications of these markers according to age.

Methods: Using single-molecule array assays, we measured neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in sera from consecutive patients with MS (n = 117) and NMOSD (n = 63). For each disease, we assessed correlations between these markers and disease severity (Expanded Disability Status Scale [EDSS]) scores according to three age groups (≤44, 45-54, and ≥55 years).

Results: Although serum GFAP levels were significantly higher in patients with NMOSD than those with MS, levels of both serum markers revealed significant positive correlations with EDSS scores in both diseases. In MS patients, the degrees of correlation between serum NfL (or GFAP) levels and EDSS scores were similar across all age groups. However, in NMOSD patients, positive GFAP-EDSS correlations were distinctively stronger in the youngest than in the oldest group. Conversely, there were no positive NfL-EDSS correlations in NMOSD in the youngest group, but there were significant in the oldest group.

Interpretation: The degrees to which serum NfL and GFAP levels reflect disease severity vary significantly with patient age in NMOSD, but not in MS. These findings suggest that the pathological processes and progression differ between the diseases; hence, serum biomarker levels may need to be interpreted differently according to patient age and disease type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aquaporin 4 / immunology
  • Biomarkers / blood
  • Female
  • Glial Fibrillary Acidic Protein / blood*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / physiopathology*
  • Neurofilament Proteins / blood*
  • Neuromyelitis Optica / blood*
  • Neuromyelitis Optica / immunology
  • Neuromyelitis Optica / physiopathology*
  • Severity of Illness Index

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Biomarkers
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • Neurofilament Proteins
  • neurofilament protein L

Grants and funding

This work was funded by Ministry of Science and ICT, Republic of Korea grants NRF‐2018M3A9E8066249 and NRF‐2018R1C1B6008884; Asan Institute for Life Science, Republic of Korea grants 2019‐0830 and 2019‐0851; Ministry of Health & Welfare, Republic of Korea grant HI18C2383; Ministry of Health grants H, I, 1, 8, C, 2, 3, 8, and 3.