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

Journal Article (Journal Article)

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 GATA3's 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.

Full Text

Duke Authors

Cited Authors

  • Tao, Y; Zhang, X; Zivadinov, R; Dwyer, MG; Kennedy, C; Bergsland, N; Ramasamy, D; Durfee, J; Hojnacki, D; Hayward, B; Dangond, F; Weinstock-Guttman, B; Markovic-Plese, S

Published Date

  • December 2015

Published In

Volume / Issue

  • 2 / 6

Start / End Page

  • e176 -

PubMed ID

  • 26601116

Pubmed Central ID

  • PMC4645170

International Standard Serial Number (ISSN)

  • 2332-7812

Digital Object Identifier (DOI)

  • 10.1212/NXI.0000000000000176


  • eng

Conference Location

  • United States