MYELIN IN MULTIPLE-SCLEROSIS IS DEVELOPMENTALLY IMMATURE

The etiology of multiple sclerosis (MS) is considered to involve genet ic, environmental, infective, and immunological factors which affect t he integrity of a normally assembled myelin sheath, either directly or indirectly resulting in demyelination. In a correlative study involvi ng protein chemical, mass spectrometric, and electron microscopic tech niques we have determined that myelin obtained from victims of MS is a rrested at the level of the first growth spurt (within the first 6 yr of life) and is therefore developmentally immature. The data supportin g this conclusion include (a) the pattern of microheterogeneity of mye lin basic protein (MBP); (b) the NH2-terminal acylation of the least c ationic component of MBP (''C-8''); (c) the phase transition temperatu re (T-c) of myelin isolated from victims of MS correlated with the inc reased proportion of the least cationic component of MBP; and (d) immu nogold electron microscopy using an antibody specific for ''C-8'' show ed that the distribution of gold particles in a 2-yr-old infant was si milar to the distribution found in a victim of MS. We postulate that t his developmentally immature myelin is more susceptible to degradation by one or a combination of factors mentioned above, providing the ini tial antigenic material to the immune system.