title: Blocking effects of serum reactive antibodies induced by glatiramer acetate treatment in multiple sclerosis.
abstract: 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-alpha 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.
authors.affiliation: Multiple Sclerosis Research Unit, Department of Neurology, Baylor-Methodist Multiple Sclerosis Center, Baylor College of Medicine, Houston, Texas, USA. hassansalama@yahoo.com
authors.forename: Hassan H
authors.initials: HH
authors.lastname: Salama
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Ying C Q
authors.initials: YC
authors.lastname: Zang
authors.forename: Azza
authors.initials: A
authors.lastname: El-Mongui
authors.forename: Jingwu
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000096:biosynthesis / Q000097:blood*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate