Treatment of multiple sclerosis with Copaxone (COP) Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells

被引:94
作者
Farina, C
Bergh, FT
Albrecht, H
Meinl, E
Yassouridis, A
Neuhaus, O
Hohlfeld, R
机构
[1] Univ Munich, Klinikum Grosshadern, Inst Clin Neuroimmunol, D-81366 Munich, Germany
[2] Univ Munich, Klinikum Grosshadern, Dept Neurol, D-81366 Munich, Germany
[3] Max Planck Inst Neurobiol, Dept Neuroimmunol, Martinsried, Germany
[4] Max Planck Inst Psychiat, Dept Stat, D-80804 Munich, Germany
[5] Marianne Strauss Klin, Berg, Germany
关键词
multiple sclerosis; immunotherapy; copaxone; autoimmune T cells; cytokine response;
D O I
10.1093/brain/124.4.705
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Copolymer-1 (Copaxone or COP) inhibits experimental allergic encephalomyelitis and has beneficial effects in multiple sclerosis. There is presently no practical in vitro assay for monitoring the immunological effects of COP. We used an automated, computer-assisted enzyme-linked immunoadsorbent spot assay for detecting COP-induced interferon-gamma (IFN-gamma)- and interleukin-4 (IL-4)-producing cells and a standard proliferation assay to assess the immunological response to COP in peripheral blood mononuclear cells from 20 healthy donors, 20 untreated multiple sclerosis patients and 20 COP-treated multiple sclerosis patients, Compared with untreated acid healthy controls, COP-treated patients showed (i) a significant reduction of COP-induced proliferation; (ii) a positive IL-4 Elispot response mediated predominantly by CD4 cells after stimulation with a wide range of COP concentrations; and (iii) an elevated IFN-gamma response partially mediated by CD8 cells after stimulation with high COP concentrations. All three effects were COP-specific as they were not observed with the control antigens, tuberculin-purified protein or tetanus toroid, The COP-induced changes were consistent over time and allowed correct identification of COP-treated and untreated donors in most cases, We propose that these criteria may be helpful to monitor the immunological response to COP in future clinical trials.
引用
收藏
页码:705 / 719
页数:15
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