A Panel of Serum Cytokines/Chemokines Can Distinguish between Patients with Neuromyelitis Optica and Multiple Sclerosis and Identifies Potential Pathophysiological Mechanisms and Therapeutic Targets

OBJECTIVE: To determine if serum inflammatory mediators can distinguish between patients with neuromyelitis optic (NMO) and multiple sclerosis (MS).

BACKGROUND: Both NMO and MS are inflammatory demyelinating diseases of the central nervous system. Though there is often clinical overlap, aquaporin4 antibodies help distinguish in 80%. Nevertheless the underlying differences in the neuroinflammatory pathogenesis and treatment response are poorly understood. Previous studies have often focused on Asian cohorts and a few mediators. Although cerebrospinal fluid is ideal for such studies, it is difficult to obtain. We therefore assessed a broad range of serum mediators in a well-defined UK cohort.

DESIGN/METHODS: Cases were identified from a national NIHR-funded programme and defined based on established international criteria. Cases were matched for demographics and severity. 15 mediators chosen based on the literature were assessed in sera using bead array. Unsupervised hierarchical clusters, proximity matrices and heat-maps were analysed. Predictive multivariate models using the complete set of mediators were assessed using a step-wise discriminant function analysis.

RESULTS: 19 NMO cases (Aquaporin4 positive) and 10 MS cases were studied. Significant differences between the concentrations of each mediator were found for IL17a (p=0.0005); and two approached significance, G-CSF (p=0.054) and CCL4 (p=0.086). NMO was discriminated from MS in 5 cumulative steps by IL17a (p=0.008), G-CSF (p=0.001), IL9 (p=0.001), MPO (p<0.001) and CCL4 (p<0.001). 17 (89.5%) of patients were correctly identified as NMO; overall 89.7% of patients were correctly identified in the original analysis and cross-validation.

CONCLUSIONS: The serum mediator profile for NMO was significantly different from MS in a matched UK cohort. NMO was distinguished from MS by mediators associated with eosinophils and neutrophils, the two key populations, identified in NMO tissue. Though these results require validation on a prospective cohort, the potential for serum cytokine signatures to aid diagnosis, better understand pathophysiology and identify therapeutic targets is promising.