Granulocyte invasion into brain tissue is a prominent neuropathological feature of NMOSD and MOGAD, but not of MS; GFAP and S100B are known to be quantitatively increased in NMOSD vs MS and MOGAD. However, these proteins have not been evaluated as diagnostic biomarkers.

CSF levels of GAM and ADM from patients with NMOSD (n=67), MOGAD (n=6) and RRMS (n=86) were quantitated by ELISA. The association between biomarkers and disease groups was assessed in linear models. Receiver operating characteristic curves and area under the curve (AUC) were calculated to estimate the potential to differentiate NMOSD/MOGAD from RRMS. The association of biomarkers with EDSS in NMOSD and RRMS was assessed by Spearman correlation.

In acute (≤21 days post exacerbation) stages, GAM levels of NMOSD (including anti-aquaporin-4-antibody negative cases) vs RRMS (p_all<0.003), and of MOGAD (3-44 days post exacerbation) vs RRMS (p_all≤0.008, for MPO only numerically) were increased, while they were not different between NMOSD and MOGAD.

AUC values of Elastase-2, MMP-8, and TIMP-1 to differentiate NMOSD and MOGAD from RRMS were ≥0.81 and ≥0.82, respectively. The composite of S100B+GFAP_>1000pg/ml levels provided an AUC value of 0.91 to differentiate NMOSD from MOGAD. GAM levels correlated with disability scores in NMOSD (p_all≤0.002), but not in RRMS.