Treatment with glatiramer acetate induces specific IgG4 antibodies in multiple sclerosis patients.

We analysed the humoral immune response to glatiramer acetate (GA, Copaxone) in 20 multiple sclerosis patients treated with GA, 20 patients not treated with GA and 20 normal control subjects. Using an ELISA for detection of total GA-reactive immunoglobulins (all isotypes), all treated patients but also 3/20 untreated and 8/20 healthy subjects scored positive at 1:20 plasma dilutions. At higher dilutions, 5/20 treated patients and two healthy donors had relatively high levels of anti-GA antibodies. Isotype and IgG subclass analysis revealed that the two antibody-positive normal subjects had IgM and small titers of IgG1 or IgG2 antibodies. In contrast, 18 of 20 GA-treated patients, had low but significant titers of GA-reactive IgG4 antibodies. This finding is consistent with the previously described GA-mediated induction of T-helper 2 (TH2)-like regulatory T cells.