METHODS:Peripheral blood mononuclear cells were obtained from patients with brain-predominant RRMS, patients with spinal cord-predominant RRMS, and age-matched healthy controls and analyzed by enzyme-linked immunosorbent spot assays to quantify interferon gamma-secreting (Th1) and interleukin 17-secreting (Th17) cells responding directly ex vivo to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG).
RESULTS:
Although MBP and MOG elicited different responses, patients with multiple sclerosis (MS) who had spinal cord-predominant lesions exhibited significantly higher Th17:Th1 ratios in response to both MBP and MOG compared to patients with brain-predominant MS. Incorporating the cytokine responses to both antigens into logistic regression models showed that these cytokine responses were able to provide good discrimination between patients with distinct neuroinflammatory patterns.
CONCLUSIONS:Our findings suggest that the localization of lesions within the brain vs the spinal cord in patients with MS is associated with different effector T cell responses to myelin proteins. Further investigation of the relationship between T cell effector function, antigen specificities, and lesion sites may reveal features of pathogenic pathways that are distinct to patients with different neuroinflammatory patterns
The relative frequencies of MBP- and MOG-specific T cells differ among Th1 and Th17 effector subsets
For IFN-γ+ and IL-17+ PBMC responses, the frequencies of MBP-specific vs MOG-specific cells are compared for each individual in (A) healthy control, (B) brain-predominant, or (C) spinal cord–predominant multiple sclerosis patient groups. Asterisks indicate significant differences in the frequencies of MBP- vs MOG-specific responses. *p < 0.05, **p < 0.01, ***p< 0.001, Wilcoxon test, 2-sided. IFN = interferon; IL = interleukin; MBP = myelin basic protein; MOG = myelin oligodendrocyte glycoprotein; PBMCs = peripheral blood mononuclear cells.
(A) Pair-wise comparisons of the MBP-specific IFN-γ+, MBP-specific IL-17+, MOG-specific IFN-γ+, and MOG-specific IL-17+ responses are shown for all HCs (blue circles), patients with brain-predominant MS (red squares), and patients with spinal cord–predominant MS (green triangles) for whom responses to both myelin antigens were determined.