Composites of granulocyte activation markers can reliably distinguish neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS), even in patients who are anti-aquaporin-4 (AQP4) antibody negative, according to a new study published in the Journal of Neurology, Neurosurgery & Psychiatry. They, therefore, represent a novel biomarker for the disease.

Read more about the different types of NMOSD

The study also showed that granulocyte activation markers were associated with the degree of concurrent neurological impairment, thereby providing evidence for their pathogenic role and suggesting they could be a potential drug target for NMOSD.

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It is known that the invasion of granulocytes into the brain is a feature that differentiates NMOSD from MS. To explore whether granulocyte activation markers in cerebrospinal fluid could be used to distinguish between the 2 diseases and if their levels could provide clues about the degree of neurological impairment, a team of researchers led by Jens Kuhle, MD, PhD, from the University of Basel in Switzerland measured the levels of 5 granulocyte activation markers and a set of inflammatory and tissue-destruction markers that are known to be upregulated in NMOSD and MS in patients with NMOSD and relapsing-remitting MS (RRMS).

The granulocyte activation markers that the researchers investigated were neutrophil elastase, myeloperoxidase, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-8, and tissue inhibitor of metalloproteinase-1. The inflammatory and tissue-destruction markers that they examined were matrix metalloproteinase-9, neurofilament light chain, intercellular adhesion molecule-1, glial fibrillary acidic protein, vascular cellular adhesion molecule-1, and S100B.

They found that in patients with acute NMOSD, levels of granulocyte activation markers and adhesion molecules were higher than those in patients with MS and correlated with the patients’ clinical disability scores. The levels of other markers were similar between patients with NMOSD and RRMS. 

Peak levels of granulocyte activation markers were recorded at the onset of NMOSD attacks. In patients with MS, levels were low and stable. This allowed the differentiation of the 2 diseases for up to 21 days from the onset of clinical exacerbation. 

The composites of granulocyte activation markers provided a specificity of 76% to 100% and a sensitivity of 87% to 100% in differentiating NMOSD from MS, including anti-AQP4 antibody-negative NMOSD patients.

“There is a need to expand the database of the capacity of [granulocyte activation markers] to identify [anti-AQP4] NMOSD, as the number of patients is currently small,” according to the authors.


Leppert D, Watanabe M, Schaedelin S, et al. Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis. J Neurol Neurosurg Psychiatry. Published online April 19, 2023. doi:10.1136/jnnp-2022-330796