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Tao Y, Zhang X, Zivadinov R, et al. Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e176doi: 10.1212/NXI.0000000000000176.
Tao, Y., Zhang, X., Zivadinov, R., Dwyer, M. G., Kennedy, C., Bergsland, N., Ramasamy, D., Durfee, J., Hojnacki, D., Hayward, B., Dangond, F., Weinstock-Guttman, B., & Markovic-Plese, S. (2015). Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS. Neurology(R) neuroimmunology & neuroinflammation, 2(6), e176. https://doi.org/10.1212/NXI.0000000000000176
Tao, Yazhong, et al. "Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS." Neurology(R) neuroimmunology & neuroinflammation vol. 2,6 (2015): e176. doi: https://doi.org/10.1212/NXI.0000000000000176
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. Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. 2015 Nov 12;2(6):e176. doi: 10.1212/NXI.0000000000000176. eCollection 2015 Dec. PMID: 26601116; PMCID: PMC4645170.
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Neurol Neuroimmunol Neuroinflamm. 2015 Nov 12;2(6):e176. doi: 10.1212/NXI.0000000000000176. eCollection 2015 Dec.

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

Neurology(R) neuroimmunology & neuroinflammation

Yazhong Tao, Xin Zhang, Robert Zivadinov, Michael G Dwyer, Cheryl Kennedy, Niels Bergsland, Deepa Ramasamy, Jacqueline Durfee, David Hojnacki, Brooke Hayward, Fernando Dangond, Bianca Weinstock-Guttman, Silva Markovic-Plese

Affiliations

  1. Departments of Neurology (Y.T., X.Z., S.M.-P.) and Microbiology and Immunology (S.M.-P.), University of North Carolina at Chapel Hill; Buffalo Neuroimaging Analysis Center (R.Z., M.G.D., C.K., N.B., D.R., J.D.), Department of Neurology (R.Z., M.G.D., C.K., N.B., D.R., D.H., J.D., B.W.-G.), State University of New York at Buffalo; and EMD Serono, Inc. (B.H., F.D.), Rockland, MA.

PMID: 26601116 PMCID: PMC4645170 DOI: 10.1212/NXI.0000000000000176

Abstract

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.

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