Long-term treatment of multiple sclerosis with glatiramer acetate: natural history of the subtypes of anti-glatiramer acetate antibodies and their correlation with clinical efficacy.
A retrospective phase IV study was designed to evaluate the anti-GA antibody subtypes, test their in vitro neutralizing activity and correlate these parameters with the clinical efficacy, in long-term GA treatment of MS patients. Serum samples from 153 MS patients, 126 treated with GA for 2 to 15 years (mean 6.6 years) and 27 treated for <2 years, were collected. Anti-myelin basic protein (MBP) and anti-GA antibodies were measured by specific ELISA. Neutralizing activity was determined by the capacity of the serum to inhibit the proliferation of GA-specific T-cells. Anti-GA antibodies were detected even after very long treatment periods, although at lower levels. Anti-MBP reactivity remained consistently negative. The IgG2 isotype of anti-GA antibodies and the multiple sclerosis severity scale (MSSS) was lower in the long-term treated patients P=0.0003 and 0.016 respectively. The neutralizing activity of anti-GA antibodies was insignificant. Our results indicate that the clinical efficacy of GA treatment could be associated with a decrease in anti-GA IgG2 isotype in long-term GA-treated patients.
Department of Neurology Hadassah-Hebrew University Medical Center, Jerusalem, 91120, Israel.
Dimitros
D
Karussis
Dvora
D
Teitelbaum
Camille
C
Sicsic
Talma
T
Brenner
D000328:Adult; D000888:Antibodies, Anti-Idiotypic; D057134:Antibodies, Neutralizing / Q000032:analysis / Q000097:blood* / Q000145:classification; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D004334:Drug Administration Schedule; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000494:pharmacology; D007557:Israel; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013995:Time; D013997:Time Factors; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D010455:Peptides; D000068717:Glatiramer Acetate