Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In experimental allergic encephalomyelitis (EAE) myelin basic protein (MBP) specific T cells differ in their encephalitogenic potential. To investigate the functional diversity of human MBP specific T cell lines, we analysed their cytotoxic activity against human astrocytes and monocytes. Five out of 14 MBP specific T cell lines killed astrocytes in the presence of MBP. Nevertheless, all lines lysed blood derived monocytes. T cell lines that lysed astrocytes efficiently in the presence of MBP, recognized peptide aa 80-99/86-105 in context with HLA-DRB5 * 0101, peptide aa 50-69/61-83 in context with HLA-DRB1 * 1501 and peptides aa 139-153, and aa 148-162 in context with HLA-DRB1 * 0101. There was no correlation of MBP-mediated lysis of astrocytes with TCR-Vbeta usage, HLA-restriction and the production of tumor-necrosis-factor-alpha (TNF-alpha), lymphotoxin (LT) and interferon-gamma (IFN-gamma). Different lysis of astrocytes, however, revealed a functional heterogeneity of MBP specific T cells, which was not observed by using monocytes as targets.
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PMID:Human myelin basic protein specific T cell lines display differential cytotoxicity against astrocytes, but are consistently cytotoxic against monocytes. 968 30

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.
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PMID:Association of HLA and T-cell receptor gene polymorphisms with Semple rabies vaccine-induced autoimmune encephalomyelitis. 1031 81

The work was done to study immunogenetic peculiarities of neuroinflammatory diseases among Korean children. A total of 13 children with neuroinflammatory diseases (8 males and 5 females; mean age 4.6 +/-2.6 yr) were consecutively recruited. Geno-mic typing was performed on their HLA DRB/HLA DQB genes using PCR-SSOP/SSP techniques with gel immunoelectrophoresis. The frequencies of HLA-DR1 *15 in children with acute disseminated encephalomyelitis (ADEM) (31%) and DQB1 *06 in other neuroinflammatory diseases (38%) were significantly increased compared with control subjects. The frequencies of HLA-DRB3 * 0202 (100%), HLA-DRB1 * 1302 (67%), HLA-DRB3 * 0301 (67%), and HLA-DQB1 * 0301 (67%) were significantly increased in children with multiple sclerosis and the frequencies of HLA-DRB1 * 1501 (40%) and HLA-DRB5 * 0101 (40%) were significantly increased in children with ADEM. HLA-DRB1 * 1401, HLA- DRB3 * 0202, and HLA-DQB1 * 0502 were found in children with acute necrotizing encephalopathy. In conclusion, HLA-DR1 * 15 and DQB1 * 06 may be involved in susceptibility to inflammation in Korean children. The frequencies of HLA-DRB1 * 1501, HLA-DRB5 * 0101, HLA-DRB3 * 0301, and HLA-DQB1* 0602 were not as high in Korean children with multiple sclerosis as in western children. However, HLA-DRB3 * 0202 was seen in all children with multiple sclerosis. Our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in Korean is distinctly different from the ones in western countries. Further studies are necessary to confirm this finding.
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PMID:Molecular analysis of HLA class II-associated susceptibility to neuroinflammatory diseases in Korean children. 1520 11

Genetic susceptibility to multiple sclerosis (MS) is associated with the MHC located on chromosome 6p21. This signal maps primarily to a 1-Mb region encompassing the HLA class II loci, and it segregates often with the HLA-DQB1*0602, -DQA1*0102, -DRB1*1501, -DRB5*0101 haplotype. However, the identification of the true predisposing gene or genes within the susceptibility haplotype has been handicapped by the strong linkage disequilibrium across the locus. African Americans have greater MHC haplotypic diversity and distinct patterns of linkage disequilibrium, which make this population particularly informative for fine mapping efforts. The purpose of this study was to establish the telomeric boundary of the HLA class II region affecting susceptibility to MS by assessing genetic association with the neighboring HLA-DRB5 gene as well as seven telomeric single nucleotide polymorphisms in a large, well-characterized African American dataset. Rare DRB5*null individuals were previously described in African populations. Although significant associations with both HLA-DRB1 and HLA-DRB5 loci were present, HLA-DRB1*1503 was associated with MS in the absence of HLA-DRB5, providing evidence for HLA-DRB1 as the primary susceptibility gene. Interestingly, the HLA-DRB5*null subjects appear to be at increased risk for developing secondary progressive MS. Thus, HLA-DRB5 attenuates MS severity, a finding consistent with HLA-DRB5's proposed role as a modifier in experimental autoimmune encephalomyelitis. Additionally, conditional haplotype analysis revealed a susceptibility signal at the class III AGER locus independent of DRB1. The data underscore the power of the African American MS dataset to identify disease genes by association in a region of high linkage disequilibrium.
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PMID:Uncoupling the roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis. 1883 4