Antibody Mediated Demyelination

Abstract

Intrathecal oligoclonal IgG antibodies (Abs) are present in more than 90% of multiple sclerosis (MS) patients and the presence of such Abs serves as a laboratory marker supporting the diagnosis of this disease. The intrathecal IgG fractions contain Abs with many different specificities, including myelin-specific Abs. Reports on anti-myelin Abs in cerebrospinal (CSF) and sera are controversial [1-7]. Several reports describe the presence of anti-myelin Ab in serum and CSF, whereas others find anti-myelin Abs only in the CSF, and yet others report that anti-myelin Abs are absent in MS patients. However, B lymphocytes specific for, and plasma cells secreting Abs to myelin basic protein (MBP), myelin-associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP) are consistently detected in the central nervous system (CNS) of MS patients [8-11]. Such cells are even found in the CSF in the absence of anti-myelin Abs, suggesting that antibodies rapidly bind to target structures, such as the corresponding auto-antigens or to Fcreceptors, and therefore become undetectable [8, 9]. In organotypic, myelinated cultures of CNS tissue, sera of MS patients promoted myelin breakdown [12]. Similar results were obtained using rabbit anti-galactocerebroside (GalC) sera and anti-whole myelin sera [13, 14]. Genain et al. [15] identified auto-antibodies against MOG within acute MS lesions, where they were associated with damaged myelin membranes, and within macrophages ingesting myelin [15]. Lassmann et al. [16] described abundant deposition of immunoglobulins in a subclass of active MS.

^* This work has already been partially published in J Neuroimmunol 1999, 101:61-67