DX61
Changes in Immunological Biomarkers in Patients with Relapsing–Remitting Multiple Sclerosis Treated with Interferon Beta-1a

Thursday, May 29, 2014
Trinity Exhibit Hall
Silva Markovic-Plese, MD , University of North Carolina at Chapel Hill, Chapel Hill, NC
Yazhong Tao, PhD , University of North Carolina at Chapel Hill, Chapel Hill, NC
Xin Zhang, MD , University of North Carolina at Chapel Hill, Chapel Hill, NC
Bianca Weinstock-Guttman, MD , Department of Neurology, State University of New York at Buffalo, Buffalo, NY
Robert Zivadinov, MD, PhD , Department of Neurology, State University of New York at Buffalo, Buffalo Neuroimaging Analysis Center, Buffalo, NY
Brooke Hayward, SM, MBA , EMD Serono, Inc., Rockland, MA
Fernando Dangond, MD , EMD Serono, Inc., Rockland, MA



Background: Shifting from a Th17- or Th1- to a Th2-cytokine profile may ameliorate relapsing–remitting multiple sclerosis (RRMS) disease activity.

Objectives: Compare percentages of CD4+ T-cells producing Th17/Th2 and Th1/Th2 cytokines and transcription factor gene expression ratios in RRMS patients versus healthy controls (HCs); measure changes in these biomarkers following 6 months’ treatment with interferon (IFN) beta-1a subcutaneously (SC).

Methods: Blood samples were collected from 15 HCs at baseline, and from 23 RRMS patients at baseline and after 6 months’ treatment with IFN beta-1a SC three times weekly (NCT01085318). The percentage of CD4+ T-cells expressing a cytokine protein of interest was determined by flow cytometry (FACS); relative gene expression, normalized against 18S mRNA, was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Differences in immunological biomarker ratios between RRMS patients and HCs at baseline, and changes over 6 months in RRMS patients after IFN beta-1a treatment, were analyzed post-hoc using Student’s t-tests.

Results: At baseline, interleukin (IL)-21/IL-4 and IL-22/IL-4 expression ratios in CD4+ T-cells were significantly higher in RRMS patients than HCs (fold difference of 1.6–4.6; p<0.05). IL-17F/IL-4 gene expression ratio was also higher (5-fold) in RRMS patients than HCs (p=0.005). In RRMS patients, after 6 months’ IFN beta-1a SC treatment, protein and gene expression ratios for IL-17F/IL-4, protein expression for IL-22/IL-4 and gene expression for IL-21/IL-4 decreased significantly (p<0.005) to HC baseline values. Although T-bet/GATA-3 gene expression ratios did not differ between RRMS patients and HCs, this ratio in patients decreased 40-fold after IFN beta-1a SC (p=0.0002).

Conclusions: Reduction of ratios of pro-inflammatory to anti-inflammatory cytokine expression, and of Th1 to Th2 transcription factor gene expression, in CD4+ T-cells in RRMS patients following 6 months’ IFN beta-1a SC treatment suggests they could be used as potential biomarkers of the therapeutic efficacy of IFN beta-1a in RRMS patients.

See more of: Disease Management, Mechanisms, and Treatment (Poster)
See more of: CMSC
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