Autoantibodies To Cerebrovascular Endothelial Cells In Virus-Induced Demyelination

Abstract

The elucidation of the pathogenesis of multiple sclerosis (MS) has been an ongoing process for many years. MS is a relapsing disease with demyelination of the central nervous system's (CNS) white mater; symptoms are motor weakness, impaired eyesight, diplopia, spasticity, lack of sensation, and many other neurological manifestations. Scientists employ animal models to study the demyelinating process, and the two most widely used animal models simulating MS are experimental allergic encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus (TMEV). Our research focused on TMEV and its pathogenesis. We performed intracerebral infection of TMEV in CBA mice. The demyelination of the CNS brought about spasticity and paralysis of the hind limbs. Many have challenged and questioned the notion whether MS and Theiler's murine virus disease (TVID) are autoimmune diseases. There have been reports of autoantibodies against the endothelial cells (Tanaka et ai, 1987) and myelin basic protein (MBP) (Cash et al., 1992) in the sera of MS patients and mouse myelin (Welsh et aI., 1987) and MBP (Rauch et aI., 1987) in the sera of TMEV infected mice. Enzyme linked immunoabsorbant assay (ELISA) was used to determine if the pathogenesis of this virus involved the production of autoantibodies to cerebrovascular cells (CVE). We made sera dilutions of 1:200 and 1:400 and performed ELISA's on the sera of numerous mice. There were significantly higher amounts of antibody binding (95% confidence) in infected and sick sera as compared to the control sera. This indicated the presence of autoantibodies to CYE in Theiler's infected mice. These results encourage the thought that autoimmunity is involved in MS and TVID either as a primary or secondary phenomenon. Such information may some day provide an answer for treating or preventing MS and other demyelinating diseases.