Neutrophil granulocyte (NG)-specific biomarkers have high sensitivity and specificity for rapid differentiation between acute neuromyelitis optica spectrum disorders (NMOSD), anti-MOG-antibody associated disease (MOGAD), and relapsing-remitting MS [1]. NG biomarkers can be measured within a few hours and may support decision making for acute therapeutic intervention.

The diagnostic gold standard for NMOSD and MOGAD is measuring AQP4 and MOG antibodies, but sensitivity is limited and laboratory turnaround time is up to 2 weeks. There is a need for better and also quicker tests, as “time is brain”, explained Dr David Leppert (University Hospital Basel, Switzerland). The objective of this study was to test whether NG-derived biomarkers in cerebrospinal fluid (CSF) could be used to differentiate NMOSD and MOGAD from MS.

CSF samples were available of 42 patients with NMOSD (18 acute, 24 stable), 6 with MOGAD, and 41 with relapsing-remitting MS (18 acute, 23 stable). A total of 4 NG-markers were measured: elastase, MPO, MMP-8, and NGAL. They were compared with 2 known markers of neuronal (NfL) and astrocyte (GFAP) damage in NMOSD and MS, and with an additional astrocytic marker, S100B. CSF from 25 healthy controls served as reference.

NG-markers appeared both in NMOSD and MOGAD. Their levels correlated both to the highest and lowest NG cell count in CSF. In acute NMOSD, all 4 NG markers were increased compared with healthy controls and acute relapsing-remitting MS (all P<0.01). In MOGAD, elastase, MPO, and MMP-8 were increased versus healthy controls (P<0.025) and acute relapsing-remitting MS (P<0.04). GFAP levels were increased only in NMOSD, mainly in the acute phase (P<0.01). NfL was elevated in all disease groups versus healthy controls (P<0.01). Neither of these 2 biomarkers are suitable to distinguish between NMOSD and MS, but they are useful disease activity markers. In acute NMOSD, S100B and GFAP levels were increased in 89% (AUC=0.82) and 83% (AUC=0.80) of patients, respectively, compared with median values of MOGAD. As such, increased S100B and GFAP levels differentiated acute NMOSD from MOGAD.

Dr Leppert concluded that NG-specific biomarkers correlate with current EDSS scores in NMOSD and can be used for rapid differentiation of acute NMOSD and MOGAD from acute relapsing-remitting MS, even in auto-antibody-negative cases. However, the sensitivity/specificity profile of these markers in this respect is currently not as good as the gold standard.

 

  1. Leppert D. MSVIRTUAL2020, Abstract LB01.03.