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  Immunological assay for assessing the efficacy of glatiramer acetate (Copaxone) in multiple sclerosis - A pilot study

Farina, C., Wagenpfeil, S., & Hohlfeld, R. (2002). Immunological assay for assessing the efficacy of glatiramer acetate (Copaxone) in multiple sclerosis - A pilot study. Journal of Neurology, 249(11), 1587-1592.

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Farina, C.1, Author           
Wagenpfeil, S.2, Author
Hohlfeld, R.1, Author           
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              
2Univ Munich, Klinikum Grosshadern, Inst Clin Neuroimmunol,; Marchioninistr 15, D-81366 Munich, Germany; Univ Munich, Klinikum Grosshadern, Inst Clin Neuroimmunol, D-81366 Munich, Germany; Max Planck Inst Neurobiol, Dept Neuroimmunol, Martinsried, Germany; Tech Univ Munich, Inst Med Stat & Epidemiol, D-8000 Munich, Germany, ou_persistent22              

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Free keywords: multiple sclerosis; glatiramer acetate; elispot assay
 Abstract: Recently we described an enzyme-linked immunoadsorbent spot (ELISPOT) assay allowing us to define an immunological response profile observed in multiple sclerosis patients treated with Copaxone (glatiramer acetate; GA) but not untreated subjects [4]. The profile encompasses three criteria, a) reduced proliferative response to GA (as observed with a standard primary proliferation assay); b) strong in vitro activation of interferon-gamma-producing T cells at high concentrations of GA (as detected by interferon-gamma ELISPOT); and c) activation of interleukin-4-producing T cells over a wider range of concentrations of GA (as detected by interleukin-4 ELISPOT). It is at present unknown whether the immunological response to GA correlates with the clinical response. To address this question we performed the pilot study reported here. We asked the major German multiple sclerosis centres to send us blood samples from all GA-treated patients who were going to discontinue treatment because of treatment failure. The clinical nonresponders either had an unchanged or increased exacerbation rate, or developed a secondary progressive course during GA treatment. Over more than one year, we prospectively collected 9 samples from clinical non-responders. We compared the immune response to GA of peripheral blood mononuclear cells from the 9 clinical nonresponders with 15 clinical responders, using a standard proliferation assay combined with ELISPOT assays for detection of interferon-gamma and interleukin-4 secreting cells. Thirteen (86%) of the 15 clinical responders met at least 2 of the immunological response criteria mentioned above. In contrast, only 2 (22%) of the 9 clinical nonresponders met two of the immunological criteria (p = 0.0006). We conclude that the ELISPOT assay may provide a promising additional tool for monitoring the treatment response in multiple sclerosis patients treated with GA.

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Language(s): eng - English
 Dates: 2002-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 10455
ISI: 000179246800015
 Degree: -

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Title: Journal of Neurology
  Alternative Title : J. Neurol.
Source Genre: Journal
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Pages: - Volume / Issue: 249 (11) Sequence Number: - Start / End Page: 1587 - 1592 Identifier: ISSN: 0340-5354