Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS

2015 
Objectives: To assess potential roles of effector cells and immunologic markers in demyelinating CNS lesion formation, and their modulation by interferon β-1a (IFN-β-1a). Methods: Twenty-three patients with relapsing-remitting multiple sclerosis (RRMS) received IFN-β-1a for 6 months. Immunologic marker results were correlated with brain MRI lesion volumes, and volumes of normal-appearing brain tissue (NABT) with decreasing or increasing voxel-wise magnetization transfer ratio (VW-MTR), suggestive of demyelination and remyelination, respectively. Results: Baseline expression of Th22 cell transcription factor aryl hydrocarbon receptor (AHR) and interleukin (IL)-17F, and percentages of IL-22–expressing CD4 + and CD8 + cells, were significantly higher in patients vs 15 healthy controls; IL-4 in CD4 + cells was lower. Baseline percentage of IL-22–producing CD8 + cells positively correlated with T2 lesion volumes, while percentage of IL-17A–producing CD8 + cells positively correlated with T2 and T1 lesion volumes. IFN-β-1a induced reductions in transcription factor AHR, T-bet, and retinoic acid–related orphan nuclear hormone receptor C (RORc) gene expression, while it increased GATA39s expression in CD4 + cells. Percentages of IL-22-, IL-17A-, and IL-17F-expressing T cells significantly decreased following treatment. Increased percentages of IL-10–expressing CD4 + and CD8 + cells correlated with greater NABT volume with increasing VW-MTR, while decreased percentage of IL-17F–expressing CD4 + cells positively correlated with decreased NABT volume with decreasing VW-MTR. Conclusions: Findings indicate that IFN-β-1a suppresses Th22 and Th17 cell responses, which were associated with decreased MRI-detectable demyelination. Classification of evidence: This pilot study provides Class III evidence that reduced Th22 and Th17 responses are associated with decreased demyelination following IFN-β-1a treatment in patients with RRMS.
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