RT Journal Article
SR Electronic
T1 Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e176
DO 10.1212/NXI.0000000000000176
VO 2
IS 6
A1 Yazhong Tao
A1 Xin Zhang
A1 Robert Zivadinov
A1 Michael G. Dwyer
A1 Cheryl Kennedy
A1 Niels Bergsland
A1 Deepa Ramasamy
A1 Jacqueline Durfee
A1 David Hojnacki
A1 Brooke Hayward
A1 Fernando Dangond
A1 Bianca Weinstock-Guttman
A1 Silva Markovic-Plese
YR 2015
UL http://nn.neurology.org/content/2/6/e176.abstract
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