Distinct T cell signatures define subsets of patients with multiple sclerosis.
OBJECTIVE
We investigated T cell responses to myelin proteins in the blood of healthy controls and 2 groups of patients with relapsing-remitting multiple sclerosis (RRMS) who exhibited lesions either predominantly in the brain or predominantly in the spinal cord in order to assess whether distinct neuroinflammatory patterns were associated with different myelin protein-specific T cell effector function profiles and whether these profiles differed from healthy controls.


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.
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
Mark C
MC
Johnson
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
Emily R
ER
Pierson
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
Andrew J
AJ
Spieker
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
A Scott
AS
Nielsen
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
Sylvia
S
Posso
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
Mariko
M
Kita
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
Jane H
JH
Buckner
Departments of Immunology (M.C.J., E.R.P., J.M.G.) and Biostatistics (A.J.S.), University of Washington, Seattle; Neuroscience Institute (A.S.N., M.K.), Virginia Mason Medical Center, Seattle; and Translational Research Program at the Benaroya Research Institute at Virginia Mason (S.P., J.H.B.), Seattle, WA.
Joan M
JM
Goverman