Abstract
Abstract The determination of the pathogenic role of autoantibody (AuAb) is a challenge in any autoimmune disease, such as multiple sclerosis (MS). This project used Theiler's virus-induced disease to characterize the AuAbs produced in the central nervous system (CNS) by antibody-secreting cells (ASCs). Mice infected with Theiler's murine encephalitis virus (TMEV) develop an immune-mediated demyelinating disease (TIDD), characterized by progressive weakness, CNS inflammation and demyelination, which represents an excellent model of MS. Flow Cytometry (FACS), ELISpot, and real-time RT-PCR, were used to characterize ASCs and their antibody production in the CNS, and ELISA and immunohistochemistry (IHC) were used to identify autoantibodies and their deposition. We found that ASCs in the CNS were CD138 positive, readily visualized as IgG+ by IHC, and commonly found in clusters of cells in the CNS. AuAbs to CNS antigens were present in the sera, and antibody was deposited in the spinal cord of TIDD mice. The blood-brain barrier, measured by CSF albumin index and Evans Blue injection, was intact. This study analyzes CNS ASCs and autoantibodies with specificity toward CNS antigens in TIDD, and raises the possibility that AuAb may significantly contribute to disability in this model. This work was supported by the New Jersey Commission on Spinal Cord Research.
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