Abstract

Abstract Objective: To identify predictive immunological biomarkers in patients with relapsing-remitting multiple sclerosis (RRMS) correlating with brain magnetization transfer imaging measures. Background: Baseline immunological biomarkers may help predict response to treatment. Methods: Intracellular cytokine staining and gene expression studies were performed on CD4+ and CD8+ T cells derived from 23 patients with RRMS and 15 healthy controls (HCs) at baseline (BL) and 6 months after subcutaneous interferon (IFN) β-1a treatment. The correlation between the changes in volume of normal-appearing brain tissue (NABT) and T2 lesion volume (LV) measured by voxel-wise magnetization transfer ratio (VW-MTR) with BL immunological parameters was investigated. Results: The percentage of BL IL-22-positive T cells was higher in patients than in HCs (CD8+, p=0.008; CD4+, p=0.039). A higher percentage of IL-22-positive CD8+ cells at BL correlated with a greater amount of decreasing VW-MTR T2 LV (p=0.031) in treated patients at 6 months, consistent with more prominent demyelination in T2 lesions, and a higher percentage of IFN-γ-positive CD8+ cells at BL correlated with a greater amount of decreasing VW-MTR NABT volume (p=0.007), consistent with more prominent demyelination in NABT. Conclusions: Production of IL-22 and IFN-γ by CD8+ cells is predictive of more prominent demyelinating changes.

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