ABSTRACT
Multiple sclerosis (MS), characterized by neurological impairment of varying severity, is a human disease prototypic of immune-mediated brain tissue damage which presents as demyelinating lesions or ‘plaques’. Autoimmune T-cells specific for myelin antigens are present at higher frequency in the immune repertoire of MS patients and are believed to be the basis for the immune-mediated pathogenesis of the disease. However, circumstantial, as well as experimental, evidence suggests that cellular immune effector mechanisms cannot solely account for the extensive destruction of myelin typical of MS, and it is likely that humoral immune effector mechanisms are also involved in disease pathogenesis. A biochemical marker for MS is an elevated level of immunoglobulins (Igs) in brain tissue and cerebrospinal fluid (CSF), which results mostly from intrathecal synthesis.1 Myelinotoxicity of MS CSF and brain extract has been demonstrated,1 and Igs isolated from MS, but not control brain tissue, were shown to stimulate the degradation of myelin basic protein (MBP) in human myelin.2 That IgG possibly directed against some component of myelin participates locally in myelin breakdown in MS was suggested by the study of Prineas and Graham,3 where capping of surface IgG was observed only on macrophages involved in myelin breakdown at plaque margins. Despite intensive work carried out to determine the specificity of Igs present in MS central nervous system (CNS), the target antigens are known for only a small proportion of the intrathecally synthesized Igs. Among these, myelin and viral components, particularly those cross-reacting with myelin antigens, would be of particular importance in antibody-mediated demyelination.
