Nicole Kerlero de Rosbo and Avraham Ben-Nun, ISRAEL

A biochemical marker for multiple sclerosis (MS) is an elevated level of immunoglobulins (Igs) in brain tissue and cerebrospinal fluid, which results mostly from intrathecal synthesis. Igs isolated from brain tissue have been shown to cause demyelination in vitro, suggesting their possible pathogenic role in vivo. Although humoral responses to a number of myelin and non-myelin antigens have been demonstrated in MS, the target(s) recognized by demyelinating MS Igs have not been identified. In vitro studies have indicated that, while antibodies raised against myelin basic protein (MBP), proteolipid protein (PLP) or myelin-associated glycoprotein (MAG) do not induce demyelination, antibodies specific for myelin surface antigens, in particular myelin oligodendrocyte glycoprotein (MOG), are extensively demyelinating. These data are corroborated by in vivo studies in experimental autoimmune encephalomyelitis (EAE), whereby injection of anti-MOG antibody in animals with EAE induced by encephalitogens other than MOG, results in extensively demyelinated lesions. More recently, demyelination in EAE has been convincingly linked to the presence of anti-MOG antibodies in affected animals. In MS, anti-MOG antibodies are apparently more frequent than in control individuals; although their pathogenic role has yet to be established, a comparative study of acute lesions in MS patients and in marmosets has suggested that anti-MOG antibodies may be at least partly responsible for the large scale demyelination characteristic of MS.
The continuing support of our laboratory by the National Multiple Sclerosis Society of New York is gratefully acknowledged. A. Ben-Nun is the incumbent of the Eugene and Marcia Appelbaum Professorial Chair.