Ž . Journal of Neuroimmunology 115 2001 152–160 www.elsevier.comrlocaterjneuroin Humoral and cellular immune responses to Copolymer 1 in multiple sclerosis patients treated with Copaxone w Talma Brenner a , Ruth Arnon b , Michael Sela b , Oded Abramsky a , Zeev Meiner a , Rivka Riven-Kreitman c , Nora Tarcik c , Dvora Teitelbaum b, ) a Department of Neurology, Hadassah UniÕersity Hospital, Jerusalem, Israel b Department of Immunology, Weizmann Institute of Science, RehoÕot, Israel c The R & D DiÕision, TeÕa Pharmaceuticals, Netanya, Israel Received 5 July 2000; received in revised form 22 September 2000; accepted 9 January 2001 Abstract Ž Humoral and cellular immune responses were followed in multiple sclerosis patients treated with Copolymer 1 Cop1, glatiramer w . Ž . acetate, Copaxone who participated in three different clinical trials. All patients 130 developed Cop1 reactive antibodies, which peaked at 3 months after initiation of treatment, decreasing at 6 months and remaining low. IgG1 antibody levels were 2–3-fold higher Ž . than those of IgG2. The proliferative response of Peripheral Blood Mononuclear Cells PBMC to Cop1 was initially high and gradually decreased during treatment. Antibodies and T cell responses to MBP were low and did not change significantly during the treatment. The humoral and cellular immunological responses to Cop1 do not correlate with the side effects and do not affect its therapeutic activity. The preferential production of IgG1 over IgG2 antibodies may indicate that Th2 responses are involved in mediating the clinical effect of Cop1. q 2001 Published by Elsevier Science B.V. Keywords: Glatiramer acetate; Copolymer 1; Anti-Cop1 antibodies; T cell proliferation; IgG1rIgG2; Th1rTh2 1. Introduction Ž . Multiple sclerosis MS is an inflammatory disease of Ž . the central nervous system CNS , characterized by local- Ž . ized myelin destruction Hallpike, 1983 . Despite exten- sive scientific and clinical research, the aetiology and pathogenesis of MS remain largely unknown, but there are indications that the disease is of autoimmune nature. Col- lectively, studies in both the animal model, experimental Ž . autoimmune encephalomyelitis EAE and in patients indi- cate that MS is most likely the result of a primary T Ž cell-driven aberrant immune response Paterson, 1979; Martin et al., 1992; Steinman et al., 1994; Hafler and . Weiner, 1995 to a number of myelin antigens, including Ž . Ž . myelin basic protein MBP , proteolipid protein PLP and Ž .Ž myelin oligodendrocyte glycoprotein MOG Kerlero de . Rosbo et al., 1997, Diaz-Viloslada et al., 1999 . Indeed, T cells reactive to these three antigens can be retrieved from Ž . Ž blood and cerebrospinal fluid CSF of MS patients Stein- ) Corresponding author. Tel.: q 972-8-9342537; fax: q 972-9344141. Ž . E-mail address: dvora.teitelbaum@weizmann.ac.il D. Teitelbaum . man et al., 1995; Allegretta et al., 1990; Hohlfeld et al., . 1995 . However, it should be noted that autoreactive myelin-specific T cells can also be readily recovered from Ž healthy individuals Wucherpfennig et al., 1994; . Markovic-Plese et al., 1995 . In addition to the involve- ment of activated lymphocytes, myelin specific antibodies were also implicated in the pathogenesis of MS. Thus, Ž elevated levels of antibodies to both MBP and PLP War- . Ž ren et al., 1994 as well as to MOG Bernard and Kerlero . de Rosbo, 1992 , were detected in MS patients. Other studies indicated the presence of antibodies against several brain gangliosides in CSF of MS patients but not in normal Ž . individuals Arnon et al., 1980 . In view of the autoimmune nature of MS, the drugs recommended for its treatment, particularly for relapsing– remitting MS, aim at the reduction of the autoimmune responses that presumably lead to the neurological dam- age. Two types of immunoregulators have been approved for clinical use—several recombinant beta interferons and Ž the polypeptide Copolymer 1. The beta interferons IFNb- . 1b and IFNb-1a are in use in many countries worldwide. They have been shown to reduce exacerbation frequency 0165-5728r01r$ - see front matter q 2001 Published by Elsevier Science B.V. Ž . PII: S0165-5728 01 00250-8