Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis

Definition of the immune process that causes demyelination in multiple scle rosis is essential to determine the feasibility of Ag-directed immunotherap y. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset) , we show that immunization with myelin basic protein and proteolipid prote in determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glyc oprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposi tion in central nervous system white matter lesions. These data associate i ntermolecular "determinant spreading" with clinical autoimmune disease in p rimates and raise important-issues for the pathogenesis and treatment of mu ltiple sclerosis.