Journal Article

Blocking effects of serum reactive antibodies induced by glatiramer acetate treatment in multiple sclerosis

Hassan H. Salama, Jian Hong, Ying C. Q. Zang, Azza El‐Mongui and Jingwu Zhang

in Brain

Published on behalf of The Guarantors of Brain

Volume 126, issue 12, pages 2638-2647
Published in print December 2003 | ISSN: 0006-8950
Published online December 2003 | e-ISSN: 1460-2156 | DOI: https://dx.doi.org/10.1093/brain/awg269
Blocking effects of serum reactive antibodies induced by glatiramer acetate treatment in multiple sclerosis

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Glatiramer acetate (GA) is a treatment option for multiple sclerosis. Although its mechanism of action remains unclear, evidence has emerged supporting the role of GA as an immunomodulatory drug that regulates T‐cell function. It has been demonstrated that long‐term GA treatment induces a serum antibody response; however, the functional properties of these ‘reactive antibodies’ are unknown. It has been speculated that GA‐induced antibodies may have a blocking effect that can inhibit the immunologic activity of GA. This study was conducted to determine whether serum antibodies induced by GA treatment can block the in vitro immunoregulatory effects of GA on T‐cell proliferation and cytokine production. Forty‐two patients with relapsing‐remitting multiple sclerosis who were treated with GA for 1–5 years were examined for GA antibody titres using enzyme‐linked immunoabsorbent assay (ELISA). Thirty‐three percent of patients developed high antibody titres [antibody binding index (ABI) = 16–64] and 14% had low antibody titres (ABI = 4) after 1 year on treatment. Results showed that purified GA antibodies blocked the stimulatory effects of GA on GA‐specific T‐cell lines of Th0 cytokine profile. The increase in interleukin‐10 (IL‐10) and IL‐4 levels and the decrease in IL‐12 and tumour necrosis factor‐α levels, normally seen with GA stimulation, were reversed in the presence of GA antibodies. The study has important implications in our understanding of the potential role of high‐titre GA antibodies in the treatment of multiple sclerosis.

Keywords: Keywords: glatiramer acetate; Copaxone; cytokines; serum reactive antibodies; multiple sclerosis; Abbreviations: ABI = antibody binding index; CPM = counts per minute; EDSS = Expanded Disability Status Scale; ELISA = enzyme‐linked immunoabsorbent assay; GA = glatiramer acetate; HEL = hen egg lysozyme; Ig = immunoglobulin; IL = interleukin; OD = optical density; PBMCs = peripheral blood mononuclear cells; TNF‐α = tumour necrosis factor‐α

Journal Article.  5045 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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