S. Piyasirisilp et al., Association of HLA and T-cell receptor gene polymorphisms with Semple rabies vaccine-induced autoimmune encephalomyelitis, ANN NEUROL, 45(5), 1999, pp. 595-600
Semple rabies vaccine is derived from brain tissue infected with rabies vir
us that is subsequently inactivated with phenol. Semple rabies vaccine-indu
ced autoimmune encephalomyelitis (SAE) occurs in 1 in 220 immunized individ
uals. The immune response to myelin basic protein and pathological changes
of demyelination in SAE suggest that this disease is the human homologue of
experimental autoimmune encephalomyelitis (EAE). SAE and EAE are frequentl
y studied as models for the human demyelinating disease multiple sclerosis.
Major histocompatibility complex (MHC) class II and T-cell receptor (TCR)
gene polymorphisms play important roles in rodent susceptibility to EAE and
were analyzed to determine if the same was true in humans with SAE. HLA-DR
B1, HLA-DQB1, and TCRBV gene polymorphisms were studied in Thai individuals
with SAE (n = 18), with vaccination without neurological complications (n
= 43), and without vaccination (n = 140). The allele frequencies of HLA-DR9
(DRB1*0901) and HLA-DR17 (DRB1*0301) were increased in SAE patients (DR9 =
22%, DR17 = 14%) compared with vaccinated controls (DR9 = 13%, DR17 = 6%)
and with unvaccinated controls (DR9 = 9%, DR17 = 4%). The allele frequency
of HLA-DQ7 (DQB1*0301) was decreased in SAE patients (8%) compared with vac
cinated controls (15%) and with unvaccinated controls (25%). These suscepti
bilities are distinct from those associated with multiple sclerosis. The fr
equencies of TCRBV alleles and haplotypes were similar in SAE patients and
vaccinated controls. These data suggest that genetic susceptibility associa
ted with MHC class II alleles may have a role in the pathogenesis of SAE an
d its mechanism may be different from those involved in multiple sclerosis.