Treatment of multiple sclerosis with Copaxone (COP)

Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells

Cinthia Farina, Florian Then Bergh, Holger Albrecht, Edgar Meinl, Alexander Yassouridis, Oliver Neuhaus, Reinhard Hohlfeld

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

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-γ (IFN-γ)- 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 and 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-γ 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 toxoid. 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.

Original languageEnglish
Pages (from-to)705-719
Number of pages15
JournalBrain
Volume124
Issue number4
Publication statusPublished - 2001

Fingerprint

Interleukin-4
Interferons
Multiple Sclerosis
Blood Cells
Therapeutics
Glatiramer Acetate
Tissue Donors
Immunologic Monitoring
Immunosorbents
Tetanus Toxoid
Autoimmune Experimental Encephalomyelitis
Tuberculin
Clinical Trials

Keywords

  • Autoimmune T cells
  • Copaxone
  • Cytokine response
  • Immunotherapy
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Farina, C., Bergh, F. T., Albrecht, H., Meinl, E., Yassouridis, A., Neuhaus, O., & Hohlfeld, R. (2001). Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells. Brain, 124(4), 705-719.

Treatment of multiple sclerosis with Copaxone (COP) : Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells. / Farina, Cinthia; Bergh, Florian Then; Albrecht, Holger; Meinl, Edgar; Yassouridis, Alexander; Neuhaus, Oliver; Hohlfeld, Reinhard.

In: Brain, Vol. 124, No. 4, 2001, p. 705-719.

Research output: Contribution to journalArticle

Farina, C, Bergh, FT, Albrecht, H, Meinl, E, Yassouridis, A, Neuhaus, O & Hohlfeld, R 2001, 'Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells', Brain, vol. 124, no. 4, pp. 705-719.
Farina, Cinthia ; Bergh, Florian Then ; Albrecht, Holger ; Meinl, Edgar ; Yassouridis, Alexander ; Neuhaus, Oliver ; Hohlfeld, Reinhard. / Treatment of multiple sclerosis with Copaxone (COP) : Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells. In: Brain. 2001 ; Vol. 124, No. 4. pp. 705-719.
@article{74060aac0340429e8c6bc471cc26f98f,
title = "Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells",
abstract = "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-γ (IFN-γ)- 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 and 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-γ 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 toxoid. 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.",
keywords = "Autoimmune T cells, Copaxone, Cytokine response, Immunotherapy, Multiple sclerosis",
author = "Cinthia Farina and Bergh, {Florian Then} and Holger Albrecht and Edgar Meinl and Alexander Yassouridis and Oliver Neuhaus and Reinhard Hohlfeld",
year = "2001",
language = "English",
volume = "124",
pages = "705--719",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Treatment of multiple sclerosis with Copaxone (COP)

T2 - Elispot assay detects COP-induced interleukin-4 and interferon-γ response in blood cells

AU - Farina, Cinthia

AU - Bergh, Florian Then

AU - Albrecht, Holger

AU - Meinl, Edgar

AU - Yassouridis, Alexander

AU - Neuhaus, Oliver

AU - Hohlfeld, Reinhard

PY - 2001

Y1 - 2001

N2 - 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-γ (IFN-γ)- 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 and 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-γ 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 toxoid. 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.

AB - 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-γ (IFN-γ)- 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 and 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-γ 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 toxoid. 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.

KW - Autoimmune T cells

KW - Copaxone

KW - Cytokine response

KW - Immunotherapy

KW - Multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=0035049725&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035049725&partnerID=8YFLogxK

M3 - Article

VL - 124

SP - 705

EP - 719

JO - Brain

JF - Brain

SN - 0006-8950

IS - 4

ER -