UMLS:C0014070 - FACTA Search

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Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental autoimmune encephalomyelitis (EAE) was induced in inbred and congenic strains of mice by injection of mouse spinal cord homogenate (MSCH) in Freund's complete adjuvant (FCA) with pertussis vaccine. Genetic analyses showed that susceptibility to EAE in mice was inherited as a dominant trait and was in part controlled by genes located in the centromeric half of the H-2 complex. Mice with EAE developed cell-mediated immune responsiveness to basic protein of myelin (BPM), as judged by the macrophage migration inhibition assay, using peritonealyexudate cells; this was not observed with mice of resistant strains. However, the migration of peritoneal exudate cells of both susceptible and resistant strains was significantly inhibited in the presence of purified protein derivative (PPD) of M. tuberculosis. Thus, the genes involved in the control of susceptibility to EAE also influence T cell responsiveness to BPM. Antibody to BPM, as judged by radioimmunoassay, was detected in susceptible and resistant strains but there was no correlation between the presence or levels of antibody and susceptibility or resistance to EAE. It is suggested that resistance to EAE is associated with failure of T cells to recognize and/or respond to the encephalitogenic determinant of the BPM molecule.
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PMID:Experimental autoimmune encephalomyelitis in mice: genetic control of susceptibility. 110 34

Myelin/oligodendrocyte glycoprotein (MOG) is expressed specifically in the central nervous system (CNS) by myelinating glial cells, the oligodendrocytes. The external location of MOG on myelin sheaths and its late expression during myelinogenesis argue for a role of MOG in the completion of myelin and maintenance of its integrity. MOG is a target autoantigen in demyelinating diseases, such as experimental autoimmune encephalomyelitis (EAE) in animals and multiple sclerosis (MS) in humans. We previously located the gene encoding MOG to the major histocompatibility complex (MHC), both in human, by cytogenetics, and in mouse, by analysis of recombinants. To refine the position, we have now selected yeast artificial chromosome clones (YAC) which contain the MOG gene. Physical mapping of the human MOG and the mouse Mog genes by characterization of these YAC clones indicated that the gene is located at the distal end of the major histocompatibility complex (MHC) class Ib region in both species. The human MOG gene lies 60 kilobases (kb) telomeric to HLA-F in a head-to-head orientation; the mouse Mog gene lies 25 (kb) telomeric to H2-M5 in a tail-to-head orientation. These orthologous genes provide markers for comparative analysis of the evolution of the MHC in the two species. The physical mapping of MOG should facilitate analysis of its role in hereditary neurological diseases, and the YAC clones identified here will permit the identification of new genes in the region.
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PMID:Physical mapping of the human and mouse MOG gene at the distal end of the MHC class Ib region. 759 Sep 72

Pertussis toxin (PTX) is the primary component responsible for eliciting the majority of biological activities associated with Bordetella pertussis, including the induction of several tissue-adjuvant models of organ-specific autoimmune disease. PTX, when administered in vivo, enhances vascular permeability, which is made manifest by a concomitant increase in sensitivity to a variety of agents and treatments affecting the vascular bed. One such agent is histamine, and the response to PTX, as measured by hypersensitivity following vasoactive amine challenge, is genetically controlled by the Bphs locus. Susceptibility to the induction of both experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) in mice is associated with, and in the latter case linked to, a susceptible allele at this locus. We report here the mapping of the Bphs locus to mouse chromosome 6, telomeric of Tcrb and centromeric of Prp (D6Nds8). This region also contains a number of loci of immunologic relevance including Igk, Ly-2, Ly-3, Il-5r, Ly-35, Ly-4, and Tnfr-2.
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PMID:Locus controlling Bordetella pertussis-induced histamine sensitization (Bphs), an autoimmune disease-susceptibility gene, maps distal to T-cell receptor beta-chain gene on mouse chromosome 6. 847 18

Experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis, is a T cell-mediated autoimmune disease that can be induced in experimental animals by immunization with myelin Ags. Inbred strains of mice show varying degrees of susceptibility to EAE, indicating that susceptibility is an inherited trait. To define the genetic factors that control susceptibility to EAE, we performed linkage analysis on the first backcross (BC1) between highly susceptible SJL/J mice and resistant B10.S mice, both of which are of the H-2s haplotype. Mice were immunized for disease with encephalitogenic myelin proteolipid protein peptide 139 to 151, and analysis was performed on 68 backcross mice showing the severe disease phenotype (disease score > or = 3)and 68 backcross mice of the resistant phenotype (no clinical or histologic signs of disease) using microsatellite markers covering >98% of the genome. We found the strongest linkage (p = 0.001) with clinical disease at two loci: one at the telomeric end of chromosome 2, and another near the center of chromosome 3. In addition, several other regions showing some evidence of linkage (p < or = 0.05) with clinical disease were found.
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PMID:Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis in a cross between SJL/J and B10.S mice. 875 45

Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab-mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating pathology of multiple sclerosis. We report that disease susceptibility and severity are determined by MHC and MHC-linked effects on the MOG-specific B cell response that mediate severe clinical EAE in the EAE-resistant Brown Norway (BN) rat. Immunization with the extracellular domain of MOG in CFA induced fulminant clinical disease associated with widespread demyelination and with an inflammatory infiltrate containing large numbers of polymorphonuclear cells and eosinophils within 10 days of immunization. To analyze the effects of the MHC (RT1 system) we compared BN (RT1 n) rats with Lewis (LEW) (RT1 l) and two reciprocal MHC congenic strains, LEW.1N (RT1n) and BN.1L (RT1 l). This comparison revealed that disease severity and clinical course were strongly influenced by the MHC haplotype that modulated the pathogenic MOG-specific autoantibody response. The intra-MHC recombinant congenic strain LEW.1R38 demonstrated that gene loci located both within the centromeric segment of the MHC containing classical class I and class II genes and within the telomeric RT1.M region containing the MOG gene are involved in determining Ab production and disease susceptibility. This study indicates that the current T cell-centered interpretation of MHC-mediated effects on disease susceptibility must be reassessed in multiple sclerosis and other autoimmune diseases in which autoantibody is involved in disease pathogenesis.
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PMID:Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the "resistant" Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. 1038 97

Experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis, is an inducible inflammatory and demyelinating disease of the central nervous system (CNS). Susceptibility to this disease is heritable and is demonstrated by the development of an ascending paralysis accompanied by a loss in body wt 2-3 weeks following immunization with proteins derived from CNS myelin. In a previous genetic analysis of susceptibility to EAE in a cross between susceptible SJL/J mice and resistant B10.S mice, we found suggestive evidence of linkage with disease susceptibility at the telomeric end of chromosome 2 and in the central region of chromosome 3. To define these associations more precisely and to investigate the genetic factors controlling measurable phenotypes of EAE, we performed a new analysis with a larger number of mice. The results now indicate that the chromosome 2 locus significantly influences EAE-related weight loss (P = 6.7 x 10(-5)) and that the chromosome 3 locus is linked with the development of paralysis. In addition, an intriguing inheritance pattern was revealed in which female backcross mice generated from B10.S female x (B10.S x SJL/J)F(1) male parents experienced significantly more EAE-related weight loss (P = 1.2 x 10(-4)) than females generated from F1 female x B10.S male parents. After controlling for this inheritance, a new locus at the centromeric end of chromosome 8 was identified that significantly influences both the development of paralysis (P = 8.2 x 10(-6)) and the incidence of CNS inflammation (P = 7.0 x 10(-5)) in EAE.
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PMID:Identification of genetic loci associated with paralysis, inflammation and weight loss in mouse experimental autoimmune encephalomyelitis. 1122 94

Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in rats is a chronic inflammatory demyelinating disease of the central nervous system (CNS) strongly mimicking multiple sclerosis (MS). We determined the involvement of macrophages and microglia in the lesions of MOG-EAE in relation to different major histocompatibility complex (MHC, RT1 in rat) haplotypes. We used intra-RT1 recombinant rat strains with recombinations between the RT1a and RT1u haplotypes on the disease permissive LEW non-MHC genome. Activated microglia and macrophages were identified morphologically and by expression of ED1 and allograft inhibitory factor-1 (AIF-1), and differentiated by their morphological phenotype. White matter lesions contained more macrophages and less microglia compared to grey matter lesions. Similarly active lesions were mainly infiltrated by macrophages, while microglia were abundant in inactive demyelinated plaques. In addition, we found a highly significant genetic association between a macrophage or microglia dominated lesional phenotype, which was independent from location and activity of the lesions. This was not only the case in demyelinating plaques of chronic EAE, but also in purely inflammatory lesions of acute passive transfer EAE. Rat strains with an u-haplotype in both the Class II and the telomeric non-classical Class I region revealed inflammatory and demyelinating lesions, which were dominated by activated microglia. The a-haplotype in any of these regions was associated with macrophage dominated lesions. A comparison of lesions, exactly matched for stages of demyelinating activity in these different rat strains, showed that in spite of a similar extent of demyelination, axonal injury was significantly less in microglia compared to macrophage dominated lesions. Thus, our studies document a genetic influence of the MHC-region on the relative contribution of macrophages versus microglia in the pathogenesis of EAE.
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PMID:MHC gene related effects on microglia and macrophages in experimental autoimmune encephalomyelitis determine the extent of axonal injury. 1214 97

To investigate effects of a 16.8-Mb region on rat chromosome 4q42-43 on encephalomyelitis, we performed a high-resolution mapping using a 10th generation advanced intercross line between the susceptible DA strain and the MHC identical but resistant PVG.1AV1 strain. Clinical signs of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) developed in 29% of 772 F(10) rats. Three regions controlling disease, Eae20, Eae21, and Eae22, were mapped using 15 microsatellite markers spanning 16.8 Mb. Eae20 was a major genetic determinant within the region whereas Eae21 modified disease severity. Eae22 was identified as an epistatic region because it only displayed an effect together with Piebald Virol Glaxo (PVG) alleles on Eae20. Disease down-regulation by PVG alleles in the telomeric part of Eae20 was also demonstrated in DA rats made congenic for a approximately 1.44-Mb chromosomal region from PVG. As the region containing Eae20-Eae22 also regulates arthritis, together with the fact that the syntenic mouse 6F(2)-F(3) region regulates experimental lupus and diabetes, and the syntenic human 12p13.31-13.2 region regulates multiple sclerosis and rheumatoid arthritis, the present data point to genes that control several inflammatory diseases. The pairscan analyses of interaction, which here identified Eae22, are novel in the encephalomyelitis field and of importance in the design of further studies of this region in other diseases and species. The limited number of genes identified in Eae20, Eae21, and Eae22 enables focused examination of their relevance in mechanistic animal studies and screening of their association to human diseases.
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PMID:Resolution of a 16.8-Mb autoimmunity-regulating rat chromosome 4 region into multiple encephalomyelitis quantitative trait loci and evidence for epistasis. 1563 14

The major histocompatibility complex (MHC) regulates multiple sclerosis (MS) and its model experimental autoimmune encephalomyelitis (EAE). We created four new intra-MHC recombinant rat strains, between the MHC haplotypes RT1(n) (BN) and RT1(l) (LEW) on the LEW background, to define disease regulation and localization within the MHC. Immunization with recombinant myelin oligodendrocyte glycoprotein (a.a.1-125; MOG)/IFA induced EAE in strains expressing the MHC class II allele RT1.B(n), whereas strains expressing the RT1.B(l) were resistant. In myelin basic protein peptide (MBP(GP)63-88)/CFA-induced EAE, RT1.B(l) expressing strains were susceptible whereas strains expressing the RT1.B(n) were resistant. High levels of antigen-specific IFN-gamma secreting lymphoid cells and antigen-specific serum IgG antibodies were only recorded in rats with an MHC class II allele that permitted MOG- or MBP-EAE, respectively. Genetically, we localized the MHC regulation of the investigated EAE models to the central part of the MHC, containing the MHC class II (RT1.B/D) and the centromeric parts of the MHC class III. No influences were evident from the classical MHC class I (RT1.A), the telomeric parts of the MHC class III or the non-classical MHC class I (RT1.C/E/M) in contrast to previous reports. The MHC class II haplotype-specific regulation of EAE induced with two different CNS antigens demonstrates a strikingly specific MHC-association even within the same target organ.
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PMID:Disparate MHC class II haplotypes in myelin oligodendrocyte glycoprotein- and myelin basic protein-induced experimental autoimmune encephalomyelitis. 1574 54

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

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