PT - JOURNAL ARTICLE AU - Yazhong Tao AU - Xin Zhang AU - Robert Zivadinov AU - Michael G. Dwyer AU - Cheryl Kennedy AU - Niels Bergsland AU - Deepa Ramasamy AU - Jacqueline Durfee AU - David Hojnacki AU - Brooke Hayward AU - Fernando Dangond AU - Bianca Weinstock-Guttman AU - Silva Markovic-Plese TI - Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS AID - 10.1212/NXI.0000000000000176 DP - 2015 Dec 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e176 VI - 2 IP - 6 4099 - http://nn.neurology.org/content/2/6/e176.short 4100 - http://nn.neurology.org/content/2/6/e176.full SO - Neurol Neuroimmunol Neuroinflamm2015 Dec 01; 2 AB - 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.AHR=aryl hydrocarbon receptor; BDNF=brain-derived neurotrophic factor; FLAIR=fluid-attenuated inversion recovery; Gd=gadolinium; HC=healthy control; IFN-β-1a=interferon β-1a; IL=interleukin; MS=multiple sclerosis; NABT=normal-appearing brain tissue; NGF=nerve growth factor; PBMC=peripheral blood mononuclear cell; PD=proton density; qRT-PCR=quantitative reverse transcription–PCR; RORc=retinoic acid–related orphan nuclear hormone receptor C; RRMS=relapsing-remitting multiple sclerosis; SC=subcutaneous; TGF=transforming growth factor; TNF=tumor necrosis factor; Treg=T regulatory cell; VW-MTR=voxel-wise magnetization transfer ratio