Transfer of demyelination by intraneural injection of experimental allergic neuritis serum.

Abstract

EXPERIMENTAL allergic neuritis (EAN), an autoimmune demye-linating disease of peripheral nerve, and a model of human inflammatory polyneuritis (Guillain–Barre syndrome), can be produced by immunisation with peripheral nerve tissue in complete Freund's adjuvant (CFA)1,2. EAN, like its central nervous system counterpart, experimental allergic encephalomyelitis (EAE), has been considered as the result of cell-mediated immunity2,3, which can be transferred with lymphoid cells4,5. Sera from animals with EAN or EAE induced by whole nervous tissue antigen are capable of demyelinating myelinated organotypic cultures of peripheral or central nervous system origin, respectively6,7. The demyelinating factor in EAE sera is immunoglobulin8,9. However, little evidence has been presented to suggest that the demyelinating antibodies which can be demonstrated in vitro are involved in the pathogenesis of these diseases in vivo4,10–12. EAN and EAE have not been transferred passively with serum from affected to recipient animals by systemic4,11 or intravitreous injection12. We report here the first successful transfer of demyelination with EAN serum. Antiserum was injected directly into nerve parenchyma of recipient animals to circumvent the blood–nerve barrier. The demyelination was associated with macrophages but not with lymphocytic infiltration. The ability of sera to transfer demyelination correlated with their capacity to demyelinate cultured dorsal root ganglia. Organ specificity and complement dependency strongly suggested that the reaction was antibody-dependent and complement-mediated.