Fig. 3.

Heatmap representation of human and macaque cytokine levels at disease onset. The heatmap representing expression levels of 15 cytokines measured in plasma and the CSF of patients and animals at onset of ADS or EAE. Hierarchical clustering of cytokine levels, represented by dendrograms, were performed to gather samples having similar cytokine profiles and cytokines having similar expression patterns in the dataset. a In plasma, the hierarchical clustering defines two groups of individuals. Note that group 1 (left) gathers all samples from macaques either at the baseline or at disease onset and 1 child with MS (MS9). Group 2 (right) aggregates all other 26 humans included in this study. b In the CSF, the hierarchical clustering also defined two main groups of individuals. Group A (left) gathers five macaques at EAE onset and four children at onset of ADS MOG+; group B (right) contains all animals at base line and one EAE treated with corticoids at onset of disease, but also all patients with ADS MOG− and seven patients with ADS MOG+ (the three ON, the two NMOSD, one ADEM, one TM, and one RADS MOG+) who had elevated IL6 or G-CSF or both but in a lower magnitude as compared to patients from group A. Note that one subgroup includes the one macaque with EAE treated with corticoids and three patients with ADS MOG+. c In the CSF dosage, the hierarchical clustering restricted to the three cytokines IL6, G-CSF, and IL8 shows two main groups, group C1 (left) with all patients ADS MOG− but one, four patients with ADS MOG+ (two NMOSD (MOGR), two ON and one ADEM), and all animals at baseline; group C2 (right) includes all animals at EAE onset, seven patients with ADS MOG+ and one patient with ADS MOG− (ADEM). Each individual is represented by a number and the name of its disease. Experimental autoimmune encephalomyelitis (EAE), acute demyelinating encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), optic neuritis (ON), idiopathic transverse myelitis (TM), or MOG relapsing disease (MOGR) for atypical ADS MOG+. EAE_c refers to the CSF collected 11 days after EAE onset and treatment with 140 mg/kg of corticoids per day during the first 3 days after disease declared. (Mac) refers to healthy macaques at baseline. The sign (+) indicates patients with anti-MOG IgG