Brain, Vol. 124, No. 4, 705-719,
April 2001
© 2001 Oxford University Press
Treatment of multiple sclerosis with Copaxone (COP)
Elispot assay detects COP-induced interleukin-4 and interferon-
response in blood cells
1 Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, 2 Institute for Clinical Neuroimmunology and Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, 3 Department of Statistics, Max Planck Institute of Psychiatry, Munich, 4 Marianne-Strauss-Klinik, Berg, Germany
Correspondence to:
Dr R. Hohlfeld, Institute for Clinical Neuroimmunology, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, D-81366 Munich, Germany E-mail: hohlfeld{at}neuro.mpg.de
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-
(IFN-)- 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- 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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A Bar-Or, J Oger, E Gibbs, M Niino, T Aziz, C Renoux, S Alatab, F. Shi, D Campagnolo, F Jalili, et al. Serial combination therapy: is immune modulation in multiple sclerosis enhanced by initial immune suppression? Multiple Sclerosis, August 1, 2009; 15(8): 959 - 964. [Abstract] [PDF]
|
|
|
|
|
|
E. Thouvenot, D. Hillaire-Buys, M.A. Bos-Thompson, V. Rigau, L. Durand, B. Guillot, and W. Camu Erythema nodosum and glatiramer acetate treatment in relapsing-remitting multiple sclerosis Multiple Sclerosis, August 1, 2007; 13(7): 941 - 944. [Abstract] [PDF]
|
|
|
|
|
|
R.M. Valenzuela, K. Costello, M. Chen, A. Said, K.P. Johnson, and S. Dhib-Jalbut Clinical response to glatiramer acetate correlates with modulation of IFN-{gamma} and IL-4 expression in multiple sclerosis Multiple Sclerosis, July 1, 2007; 13(6): 754 - 762. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Hohlfeld, M. Kerschensteiner, and E. Meinl Dual role of inflammation in CNS disease Neurology, May 29, 2007; 68(22_suppl_3): S58 - S63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sarchielli, M. Zaffaroni, A. Floridi, L. Greco, A. Candeliere, A. Mattioni, S. Tenaglia, M. Di Filippo, and P. Calabresi Production of brain-derived neurotrophic factor by mononuclear cells of patients with multiple sclerosis treated with glatiramer acetate, interferon-{beta} 1a, and high doses of immunoglobulins Multiple Sclerosis, April 1, 2007; 13(3): 313 - 331. [Abstract] [PDF]
|
|
|
|
 |
|
 D. K. Tennakoon, R. S. Mehta, S. B. Ortega, V. Bhoj, M. K. Racke, and N. J. Karandikar Therapeutic Induction of Regulatory, Cytotoxic CD8+ T Cells in Multiple Sclerosis. J. Immunol., June 1, 2006; 176(11): 7119 - 7129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hong, N. Li, X. Zhang, B. Zheng, and J. Z. Zhang Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3 PNAS, May 3, 2005; 102(18): 6449 - 6454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Rauschka, C. Farina, P. Sator, S. Gudek, F. Breier, and M. Schmidbauer Severe anaphylactic reaction to glatiramer acetate with specific IgE Neurology, April 26, 2005; 64(8): 1481 - 1482. [Full Text] [PDF]
|
|
|
|
|
|
R. Hohlfeld and H. Wekerle Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines PNAS, October 5, 2004; 101(suppl_2): 14599 - 14606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Weber, M. Starck, S. Wagenpfeil, E. Meinl, R. Hohlfeld, and C. Farina Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo Brain, June 1, 2004; 127(6): 1370 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Kim, I. Ifergan, J. P. Antel, R. Seguin, M. Duddy, Y. Lapierre, F. Jalili, and A. Bar-Or Type 2 Monocyte and Microglia Differentiation Mediated by Glatiramer Acetate Therapy in Patients with Multiple Sclerosis J. Immunol., June 1, 2004; 172(11): 7144 - 7153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Salama, J. Hong, Y. C. Q. Zang, A. El-Mongui, and J. Zhang Blocking effects of serum reactive antibodies induced by glatiramer acetate treatment in multiple sclerosis Brain, December 1, 2003; 126(12): 2638 - 2647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ziemssen, T. Kumpfel, W. E. F. Klinkert, O. Neuhaus, and R. Hohlfeld Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy Brain, November 1, 2002; 125(11): 2381 - 2391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Chabot, F P Yong, D M Le, L M Metz, T Myles, and V W Yong Cytokine production in T lymphocyte-microglia interaction is attenuated by glatiramer acetate: a mechanism for therapeutic efficacy in multiple sclerosis Multiple Sclerosis, August 1, 2002; 8(4): 299 - 306. [Abstract] [PDF]
|
|