Association of HLA and T-cell receptor gene polymorphisms with semple rabies vaccine-induced autoimmune encephalomyelitis

Abstract

Semple rabies vaccine is derived from brain tissue infected with rabies virus that is subsequently inactivated with phenol. Semple rabies vaccine- induced autoimmune encephalomyelitis (SAE) occurs in 1 in 220 immunized individuals. 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 frequently 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-DRB1, 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 vaccinated controls (15%) and with unvaccinated controls (25%). These susceptibilities are distinct from those associated with multiple sclerosis. The frequencies of TCRBV alleles and haplotypes were similar in SAE patients and vaccinated controls. These data suggest that genetic susceptibility associated with MHC class II alleles may have a role in the pathogenesis of SAE and its mechanism may be different from those involved in multiple sclerosis.