Differential intrathecal inflammatory markers in acute optic neuritis and later conversion to multiple sclerosis

Background: Optic neuritis (ON) is often an early inflammatory, demyelinating event of multiple sclerosis (MS). We proffer that cytokine and chemokine profiles may (a) differ between patients with MS-related ON and those with non-MS-related ON and (b) predict conversion to MS in patients presenting with a first attack of ON. Methods: We recruited patients with acute, isolated ON as a prospective cohort between 2014 and 2016. Patients underwent clinical examination and sampling of blood and cerebrospinal fluid (CSF). Fifty-two patients with ON were included in the study. Of those, 39 patients had serum and CSF samples taken within the acute phase of onset and prior to glucocorticoid treatment (median interval from onset of symptoms 14 days, range 2-59). Twenty-six were females, 13 were males. The median age was 36 years (range 16-66). Overall, 17/39 patients were diagnosed with MS during one year follow-up. Blood and CSF IL-1β, IL-6, IL-10, IL-17, and TNF-α were measured on the highly sensitive Simoa™ platform from Quanterix, MA, US. CXCL13 was measured with an ELISA from Euroimmun, Lübeck, Germany with a stated detection limit of 10 pg/ml. For statistical analyses, multiple t-tests with Holm-Šidák correction or Fisher's exact test were used as appropriate. Results: CSF levels of TNF-α and IL-10 were significantly higher in patients who converted to MS compared to those who remained with isolated ON (TNF-α: median 0.370 pg/ml vs. 0.164 pg/ml, p=0.010; IL-10: median 0.398 pg/ml vs. 0.082 pg/ml, p=0.009). Similarly, CXCL13 in the CSF was detected more frequently in the MS-ON group than in those who did not convert (8/17 versus 2/22, p=0.0107). CSF pleocytosis, oligoclonal bands as well as increased IgG-index and albumin ratio were more frequent in patients who converted to MS than those with acute isolated ON (p< 0.0001, p=0.0013, p=0.009 and p=0.041, respectively). The cytokines IL-1β, IL-6 and IL-17 were measurable in CSF and serum, levels did not differ between groups. Conclusions: Levels of CSF TNF-α and IL-10 and CXCL13 differed between acute isolated ON patients who had converted to MS at follow-up compared to those who had not. These findings are of potential relevance to our understanding of the pathogenesis of MS and may predict conversion of ON to MS.