Study results published in Neurology Neuroimmunology & Neuroinflammation demonstrated the utility of plasma N-glycan profiles in differentiating multiple sclerosis (MS) from antibody-defined diseases such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD).

The single-center cohort study included 120 participants with either relapsing-remitting MS (RRMS, n=30), secondary progressive MS (SPMS, n=30), MOGAD (n=30), or aquaporin-4 antibody (AQP4-Ab) NMOSD (n=30). Researchers profiled plasma N-glycan levels using ultra-high-performance hydrophilic interaction liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HILIC-MS). Disease-specific glycomic signatures were assessed using orthogonal partial least-squares discriminant analysis.

Key results include the following:

  • N-glycome profiling differentiated MS vs antibody-defined diseases with 80.5% accuracy (±1.5%).
  • Within antibody-defined disorders, MOGAD and AQP4-Ab NMOSD were differentiated with 77.8% accuracy (±3.1%).
  • Within MS phenotypes, RRMS vs SPMS were distinguished with 75.2% accuracy (±3.6%).

There were 4 key discriminatory features that enabled researchers to effectively distinguish MS from antibody-defined diseases:

  • Monosialylation (OR 2.57; P<.0001)
  • Trigalactosylation (OR 2.70; P<.0001)
  • Highly branched N-glycans (OR 2.32; P=.0002)
  • Antennary fucosylation (OR 2.89; P<.0001)

These results demonstrate that plasma N-glycan signatures, which are a noninvasive and cost-effective method, may help clinicians differentiate MS from other antibody-defined diseases. The study authors note that additional research is needed to clarify the mechanistic links between glycomic alterations and disease pathology.

Source: Kacerova T, Sealey M, Saldana L, et al. Plasma N-glycan profiling enhances diagnostic precision in multiple sclerosis, AQP4-Ab NMOSD, and MOGAD. Neurol Neuroimmunol Neuroinflamm. 2025; 12(6). doi:10.1212/NXI.0000000000200502