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)

Myelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated several rat MOG cDNAs and confirmed their identity by comparison with MOG N-terminal peptide sequence. As expected, MOG mRNA expression is CNS-specific and peaks during active myelination. Our studies show that full length MOG mRNA is approximately 1.6 kb and encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24,962 MW). A single site for N-glycosylation is found at Asn-31. Rather than the ubiquitous AAUAAA polyadenylation signal, a series of three overlapping, rare poly A signals were identified. The N-terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor. This same region has 39% identity with chicken B-G antigen, a major histocompatibility complex antigen involved in B cell selection and immune repertoire development. We show that both MOG and butyrophilin, each exhibiting a single Ig-like variable region domain, meet criteria for inclusion in the immunoglobulin superfamily. Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane-spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members.
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PMID:Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily. 145 82

In addition to myelin basic protein (MBP) and proteolipid protein (PLP), oligodendrocyte (Od) membrane autoantigens, such as the glycoprotein M2/MOG, could participate in the pathogenesis of autoimmune demyelinating diseases of the central nervous system (CNS), such as experimental allergic encephalomyelitis (EAE) or multiple sclerosis (MS). We have described an Od-specific autoreactive and cytotoxic T-cell clone, named C2, which recognized M2/MOG without conventional MHC restriction. In order to analyse the Od/C2 interaction, we determined the alpha/beta T-cell receptor (TCR) variable region usages and structures of C2. Monoclonal antibody stainings of C2 and nucleotide sequences show that the alpha chain is composed of a V alpha 5 and a J alpha identical to J alpha 18BBM142 gene segments, and that the TCR beta chain is composed of V beta 17a, D beta 2.1 and J beta 2.2 gene segments indicating that C2 used a conventional alpha/beta TCR for M2/MOG recognition.
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PMID:T-cell receptor identification of an oligodendrocyte-specific autoreactive cytotoxic T-cell clone without self restriction. 146 26

The pathogenetic events leading to demyelination in experimental allergic encephalomyelitis and in human multiple sclerosis are still unclear. The involvement of anti-myelin antibodies and activated macrophages as effector cells has been postulated. We investigated the synergistic action of the monoclonal antibody 8-18C5 against myelin/oligodendrocyte glycoprotein and recombinant interferon-gamma on demyelination after simultaneous injection into the subarachnoid space of Sprague-Dawley rats. After combined injection of anti-myelin/oligodendrocyte glycoprotein antibody and interferon-gamma, electrophysiological and morphological evidence for demyelination was found. Cervical somatosensory evoked potentials and cervical short-latency somatosensory evoked potentials were significantly delayed, and the demyelinated area in the spinal cord was significantly enlarged when compared to control rats injected with either compound alone. Injection of either an irrelevant antibody and interferon-gamma or of peritoneal macrophages without anti-myelin/oligodendrocyte glycoprotein antibody and interferon-gamma did not induce demyelination. Our data suggest that the deleterious effect of interferon-gamma on multiple sclerosis may be not only due to its effect on antigen presentation but also due to potentiation of demyelination.
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PMID:Interferon-gamma potentiates antibody-mediated demyelination in vivo. 768 84

The receptor region for virus-cell interaction in Venezuelan equine encephalomyelitis (VEE) and Eastern equine encephalomyelitis (EEE) viruses was studied using a panel of 17 monoclonal antibodies (MCA). They were able to block agglutination of goose erythrocytes. The dominant role of glycoprotein E2 in the formation of viral receptor for EEE and VEE viruses was demonstrated. Competitive radioimmunoassay identified three antigenic sites in this region. These sites were also responsible for virus neutralization. MCAs to these sites protected outbred mice against lethal infection. The presence of a highly conservative region in VEE (site E2-3) and EEE (site E2a) which produced cross-reacting antibodies blocking hemagglutination of Western equine encephalomyelitis, Semliki Forest, Sindbis, Getah, Aura, Chikungunya, and Pixuna viruses was established. A hypothesis is suggested concerning the existence of similar regions for the entire alphavirus genus, and the role of this region in virus-cell interaction.
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PMID:[A monoclonal antibody study of the receptor area of the Venezuelan encephalitis virus]. 172 20

The pathogenesis of multiple sclerosis (MS) is believed to involve an autoimmune component directed against the myelin sheath. One potential target Ag for such autoimmune attack is the myelin-oligodendrocyte glycoprotein (MOG) because an anti-MOG mAb has profound influence on the course of experimental autoimmune encephalomyelitis, which to some extent represents an experimental model of MS. Using single cell assays, we have evaluated T and B cell reactivities to MOG in MS patients and controls. T cell reactivity was estimated by counting the number of cells that secreted IFN-gamma in response to MOG, whereas B cell reactivity was estimated by enumerating cells secreting antibodies that bound to MOG. MOG reactive T cells were detected in the peripheral blood of the majority of the 16 MS patients examined (mean 1/7299 mononuclear cells), but infrequently and at lower numbers in samples from neurologic controls. MOG-reactive T cells were more frequent among MS patients' cerebrospinal fluid (CSF) mononuclear cells (mean 1/450 cells). The T cell response to MOG was evidently MHC class II restricted, because Fab fragments of a rabbit polyclonal anti HLA-DR antibodies abrogated the Ag-induced increase in number of cells that secreted IFN-gamma, as analyzed on CSF and PBMC from three patients with MS. Anti-MOG IgG antibody-secreting cells were detected in blood in 8 of 16 MS patients (mean 1/25,641 cells), but they were also strongly accumulated in CSF, being detected in 8 of 10 MS patients examined (mean 1/265 cells), while rarely found in controls. The findings imply that MOG may represent a pathogenetically important target Ag in MS.
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PMID:T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis. 189 88

The CVS strain of fixed rabies virus causes acute, fatal encephalomyelitis in young adult ICR mice. Variant RV194-2, which was selected from CVS virus in cell culture with a neutralizing antiglycoprotein monoclonal antibody, has a single amino acid change in the glycoprotein. The infections caused by CVS virus and RV194-2 virus were compared in mice for 14 days postinoculation of 5 x 10(7) PFU into the right masseter muscle. All CVS virus-infected mice died (mean time to death, 7.9 days), compared with a mortality rate of 8.5% for RV194-2 virus-infected mice. RV194-2 virus spread to the ipsilateral trigeminal ganglion during the first 2 days postinoculation, and both viruses spread to the ipsilateral motor nucleus of the trigeminal nerve in the pons. Both viruses spread centrifugally and caused infection of bilateral trigeminal ganglia on day 3. The viruses spread throughout the central nervous system (CNS) at similar rates, but CVS virus infected many more neurons than did RV194-2 virus. Rabies virus antigen was observed in only occasional CNS neurons after day 6 of RV194-2 virus infection. By this time, CVS virus had caused severe widespread infection. In this model, virulence depends on improved efficiency of viral spread between CNS neurons rather than the rate of spread or topographical distribution of the infection.
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PMID:Biological basis of rabies virus neurovirulence in mice: comparative pathogenesis study using the immunoperoxidase technique. 198 16

Immunohistochemistry was used to study herpes simplex virus type 1-induced central nervous system demyelination in the trigeminal root entry zone of mice inoculated with herpes simplex virus type 1 by the corneal route. There was no change in peripheral nervous system myelin as shown by immunostaining for P0 glycoprotein. Double immunoperoxidase staining for herpes simplex virus type 1 antigens and glial fibrillary acidic protein showed that most of the infected cells were astrocytes. Glial fibrillary acidic protein immunostaining was completely lost in the inferior medial portion of the trigeminal root entry zone at 6 days after herpes simplex virus type 1 inoculation, a time when central nervous system myelin was preserved as indicated by immunostaining for myelin basic protein. The pattern of glial fibrillary acidic protein staining did not change and herpes simplex virus type 1 antigens were no longer detected after day 8. There was a progressive loss of myelin basic protein staining within the area unstained by glial fibrillary acidic protein antisera on days 8 to 14. This pattern of astrocyte loss before central nervous system demyelination is strikingly different from the reactive astrocytosis seen in other demyelinating lesions, such as acute experimental allergic encephalomyelitis, progressive multifocal leukoencephalopathy, or acute multiple sclerosis. Herpes simplex virus type 1 infection in mice provides an unusual model of acute central nervous system demyelination preceded by a loss of astrocytes.
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PMID:Early loss of astrocytes in herpes simplex virus-induced central nervous system demyelination. 204 45

MS and CIP are inflammatory diseases of the CNS and PNS that are characterized by focal demyelination. Both disorders are thought to involve autoimmune processes. The factors that lead to a chronic inflammatory process have not been completely defined, but the immune system is thought to play a prominent role as has been discussed in this chapter. The role of a persistent or recurrent viral exposure has not been reviewed here but may well be a contributing factor. Since chronic relapsing experimental encephalomyelitis in animal models is a T-cell-mediated disease that pathologically resembles MS, T cells are postulated to be of primary importance in human demyelinating diseases. Oligoclonal T-cell populations can be found in the CSF of MS patients, even though their antigenic specificity is not known. HLA associations (HLA Dw2 and HLA DR2 in MS and HLA Dw3 in chronic inflammatory neuropathy) might relate to the proposed immunopathogenesis, as class II antigens encoded by these loci might serve as restriction elements for T-cell recognition of an autoantigen by encephalitogenic cell populations. Humoral factors are thought to play an important role in the pathogenesis of CIP, as plasma exchange has been shown to be beneficial. Experimental work with an antimyelin glycoprotein monoclonal antibody demonstrates the in vivo demyelinating activity of antibodies as well as the importance of cellular elements in the demyelinating process. Finally, a number of immunoregulatory abnormalities have been demonstrated in MS patients that point to defects in immunoregulation, in particular in the generation of suppression. Decreases in AMLR in active MS might be of importance, as the AMLR is a reaction against self MHC determinants during which suppression is generated. Defects in suppression might allow self-reactive cells to escape regulation and cause inflammatory lesions in the nervous system.
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PMID:Immunologic mechanisms in chronic demyelinating diseases of the central and peripheral nervous system. 215 31

In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis. The L3T4 antigen in the mouse is analogous to the human Leu-3/T4 antigen expressed on helper T lymphocytes, because they both participate in the T cell response to class II major histocompatibility complex (MHC) antigens. Class II MHC genes and I-A antigens mediate murine experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor (AChR) autoimmunity. We studied the efficacy of mAb GK1.5 as an immunotherapeutic agent for murine EAMG. Therapy with mAb GK1.5 not only suppressed established autoimmunity to AChR but also prevented loss of muscle AChR in mice with EAMG. Moreover, permanent remission of clinical muscle weakness was induced if mAb GK1.5 therapy was initiated after the onset of clinical disease. Because the function of the Leu-3/T4 determinant on human helper T lymphocytes is analogous to the murine L3T4 determinant, use of antibody to the Leu-3/T4 determinant as an immunotherapeutic agent may provide a way to control the progression of human MG.
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PMID:Immunotherapy for myasthenia gravis: a murine model. 241 35

The encephalitogenic potential of rabies vaccines prepared from nervous tissue is a result of the presence of myelin basic protein. Vaccines prepared from duck embryos are economical and efficient, but, occasionally, cases of allergic encephalomyelitis have been reported. An improved rabies vaccine has been developed that contains the classical Pitman Moore strain of rabies virus grown in embryonated duck eggs. This vaccine has been highly purified and enriched in immunologically effective rabies virus glycoprotein antigen. We have searched for the presence of myelin basic protein using sensitive radioimmunological and immunoblotting techniques. Whereas the classical duck embryo rabies vaccine contained small amounts of myelin basic protein, in the improved purified duck embryo rabies vaccine, none could be detected.
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PMID:Absence of myelin basic protein in an improved purified duck embryo rabies vaccine. 242 9


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