MULTIPLE-SCLEROSIS - REEXPRESSION OF A DEVELOPMENTAL GENE IN CHRONIC LESIONS CORRELATES WITH REMYELINATION

Central nervous system tissue from multiple sclerosis and non-multiple sclerosis subjects was studied for the expression of exon 2 myelin ba sic protein gene products at the protein and message levels by immunoc ytochemistry and in situ hybridization, respectively. The exon 2-encod ed protein sequence is normally expressed during development (myelinat ion) within the 21 . 5- and 20 . 2-kd isoforms of myelin basic protein and is downregulated in the adult central nervous system where the 18 . 5- and 17 . 2-kd isoforms predominate, the latter devoid of exon 2 owing to alternative splicing. Exon 2 myelin basic protein gene produc ts were readily demonstrable in multiple sclerosis samples, the highes t levels correlating with remyelination in chronic lesions while norma l adult central nervous system and non-multiple sclerosis material sho wed very low levels and fetal human central nervous system tissue (a p ositive control) showed high levels. Wk conclude that recapitulation o f ontogenetic events during myelin repair accounts for the increased e xpression of the exon 2-encoded protein sequence in the adult central nervous system during multiple sclerosis, an event that might underly the previously observed T-cell activation to this protein sequence dur ing relapses.