A role of B cells and autoantibodies in disease pathogenesis is supported by numerous observations derived from a wide range of clinical, pathological, and experimental studies. Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination and axonal damage leading to chronic neurological deficits. The findings presented here may shed light on factors involved in the severity of MS and its genetics. Inter-molecular epitope spreading to neurofascin correlates with disease severity in MOG-EAE is dependent on extensive demyelination and is influenced by non-MHC genes. Anti-neurofascin IgG levels correlated with disease severity in (DAxPVG.1AV1) x DA rats, and a genomic region on chromosome 3 was found to influence this response. Spreading of the antibody response to neurofascin occurred in demyelinating MOG-induced EAE but not in EAE induced with MBP peptide 63–88. Furthermore, the anti-neurofascin IgG response was correlated with clinical parameters in 333 (DAxPVG.1AV1) x DA rats on which we performed linkage analysis to determine if epitope spreading to neurofascin was affected by non-MHC genes. We determined anti-neurofascin antibody levels during the course of disease. We used two different EAE models in DA rat one which is induced with myelin oligodendrocyte glycoprotein (MOG) which leads to disease characterized by profound demyelination, and the second which is induced with myelin basic protein (MBP) peptide 63–88 which results in severe central nervous system (CNS) inflammation but little or no demyelination. Using different EAE models, we investigated the pathophysiological basis of epitope spreading to neurofascin, a protein localized at the node of Ranvier and its regulation by non-MHC genes. Experimental autoimmune encephalomyelitis (EAE) provides an animal model that mimics MS. Ιn multiple sclerosis (MS), axonal damage leads to permanent neurological disabilities and the spreading of the autoimmune response to axonal antigens is implicated in disease progression.
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