Sustained immunological effects of Glatiramer acetate in patients with multiple sclerosis treated for over 6 years.
The availability of a group of multiple sclerosis (MS) patients at the University of Maryland, who had participated in the pivotal Copaxone trial in the early 1990s, provided an opportunity to examine the long-term immunologic effects of Glatiramer acetate (GA) treatment in MS. Forty-eight GA-reactive T-cell lines (TCL) were generated from 10 MS patients who have been receiving GA treatment for 6-9 years. Proliferative responses, cytokine production, and cross-reactivity with myelin basic protein (MBP) and the MBP immunodominant peptide 83-99 were compared to responses obtained from 10 MS patients who were tested pretreatment and after a shorter period of treatment ranging from 1 to 10 months. The results indicate that while long-term treatment with GA results in a 2.9-fold decrease in the estimated precursor frequency of GA-reactive T-cells, the sustained response to GA remains Th2-biased and in part cross-reactive with MBP and MBP (83-99) as measured by proliferation and cytokine release assays. The results indicate that despite a drop in the precursor frequency of GA-reactive T-cells with long-term treatment, the sustained response remains predominantly Th2-biased and cross-reactive with MBP, which is consistent with the anti-inflammatory effects of the drug and bystander suppression.
Chen
M
M
University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Conway
K
K
Johnson
K P
KP
Martin
R
R
Dhib-Jalbut
S
S
D015415:Biomarkers; D003429:Cross Reactions; D000068717:Glatiramer Acetate; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage*; D018418:Th2 Cells / Q000276:immunology
D015415:Biomarkers; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; C104448:myelin basic protein 83-99; D000068717:Glatiramer Acetate