B-cell responses to myelin basic protein and its epitopes in autoimmune encephalomyelitis induced by Semple rabies vaccine

Semple rabies vaccine is composed of rabies virus-infected sheep or goat br ain inactivated with phenol and is administered daily after exposure for 14 -21 days. Semple rabies vaccine-induced autoimmune encephalomyelitis (SAE) has clinico-pathological findings of demyelination similar to experimental autoimmune encephalomyelitis (EAE) caused by injection of central nervous s ystem tissue or purified myelin proteins into experimental animals and freq uently studied as a model for the human demyelinating disease, multiple scl erosis (MS). T-cell-mediated immune responses play a major role in inductio n of EAE, and antibody responses enhance disease severity. We studied the a ntibody responses to myelin basic protein (MBP) in 24 Thai patients with SA E and 77 control individuals to define the linear epitopes in human MBP tha t are encephalitogenic. Antibody levels were assessed by ELISA using native human MBP or synthetic MBP peptides of 20 amino acids. The major B-cell ep itope was MBP61-80 and a minor epitope was MBP106-140 in SAE while in MS th e major B-cell epitope is MBP84-96. MBPB1-80-specific IgG1 and IgG3 levels were significantly higher in patients than controls while IgG2 and IgG4 wer e not. The data support the hypothesis that autoreactive Th1 cells induce S AE. The difference in B-cell epitope recognition may be due to differences in the genetic backgrounds of the populations studied or may reflect underl ying differences in the pathogenesis of SAE and MS. (C) 1999 Elsevier Scien ce B.V. All rights reserved.