Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with systemic lupus erythematosus generate a sustained immune response against self. The tools of modern molecular biology have been applied to cell activities and elements/signals of the immune system, but a structural or regulatory defect has not been found. When deoxyribonucleic acids for autoantibodies were cloned and sequenced, they were like other autoantibody DNA sequences; when genetic materials for autoantibodies were inserted into transgenic mice, cells secreting the antibodies were subject to normal control mechanisms and eliminated. A failure to clear self-reactive antibody producing thymocytes has not been demonstrated in human systemic lupus erythematosus. Molecular analyses of the efferent side of the immune response have been largely normal in systemic lupus erythematosus. The structure of autoantibodies suggests that they have been generated by selection pressures and the presence of endogenous antigens. If the immune system attack on self was secondary, structural changes and metabolic reactions capable of generating antigens should be found in systemic lupus erythematosus cells. Structural changes have been found in deoxyribonucleic acid from phytohaemagglutinin-stimulated systemic lupus erythematosus lymphocytes in the form of S1 nuclease-sensitive deoxyribonucleic acid breaks. Altered cellular macromolecules could result from endogenous metabolic processes, particularly oxygen free radicals and arachidonic acid metabolites. Excess free-radical species, generating positive nitroblue tetrazolium-reacting material and positive chemiluminescence, have been found in most but not all phytohaemagglutinin-stimulated lupus lymphocyte samples. If endogenous metabolic processes act on endogenous deoxyribonucleic acid, endogenous cell DNA breakdown may lead to low molecular weight deoxyribonucleic acids and deoxyribonucleic acid/immune complexes in systemic lupus erythematosus sera that are potentially immunogenic. These combined findings suggest that the exaggerated immune responses of systemic lupus erythematosus may be a normal response to protect the host from a perceived antigenic threat.
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PMID:Molecular, metabolic and immune evidence suggest that systemic autoimmune disease is antigen-mediated. 895 98

Alterations in DNA structure by hydroxyl radical modification was characterized by UV spectroscopy, Tm, nuclease S1 digestibility and base modification. In view of indicted role of oxygen free radicals in human diseases, an attempt has been made to precisely compare the antigen binding properties of induced antibodies against hydroxyl radical modified DNA with those of naturally occurring anti-DNA autoantibodies. Antibodies induced against ROS-DNA showed diverse antigen binding characteristics which were comparable with those derived from SLE patients. The immune IgG recognized native DNA, heat denatured DNA, and synthetic polynucleotides in B-/B-like conformations. IgG isolated from SLE sera showed preference for ROS-DNA in competition-inhibition assay. The antigenic diversity of induced antibodies and preference of circulating anti-DNA autoantibodies for ROS-DNA over that of native DNA demonstrates the possible role of modified DNA antigens in the pathogenesis of SLE.
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PMID:Human anti-DNA autoantibodies and induced antibodies against ROS-modified-DNA show similar antigenic binding characteristics. 1036 60

Native human DNA was modified by ONOO- (peroxynitrite), generated by the synergistic action of sodium nitroprusside [Na2Fe(CN)5NO], an NO donor, and pyrogallol, a superoxide donor. The modifications were analysed by UV absorption characteristics, fluorescence emission transitions, nuclease S1 digestibility and melting-temperature studies. Modified DNA was found to be highly immunogenic, inducing high-titre immunogen-specific antibodies in experimental animals. A maximum of 85% inhibition of the antibody binding was observed in competition ELISA with immunogen as inhibitor. SLE (systemic lupus erythematosus) anti-DNA autoantibodies recognized modified DNA as a better antigen than the native analogue. Modification of native DNA by ONOO-, forming neo-epitopes on the molecule, may be one of the factors for the induction of the autoimmune response seen in SLE.
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PMID:Peroxynitrite-modified DNA: a better antigen for systemic lupus erythematosus anti-DNA autoantibodies. 1623 28

In the present study, the effect of singlet oxygen (1O2) (generated by ultraviolet (UV) irradiation of methylene blue) on plasmid DNA has been analyzed by UV spectroscopy, fluorescence spectroscopy, and S1 nuclease digestibility. Both native and 1O2-modified plasmid DNA were treated with a number of restriction enzymes to map out the sites damaged by 1O2. It was also observed that, on exposure to 1O2, native plasmid DNA that is non-immunogenic acquired the ability to elicit an immune response in experimental animals. However, the induced antibodies exhibited appreciable cross reactivity with various polynucleotides and nucleic acids. The data indicate that the antibodies, though cross-reactive, preferentially bind 1O2-modified epitopes on plasmid DNA. Gel retardation assay further substantiated the enhanced recognition of 1O2-modified plasmid DNA over the native form. The antibodies developed were then subjected to competition ELISA with sera from various diseases such as systemic lupus erythematosus, rheumatoid arthritis, and cancer. These results suggest that upon exposure of DNA to 1O2, neo-epitopes are generated, which may be one of the factors for the induction of circulating autoantibodies in the three diseases.
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PMID:Plasmid DNA acquires immunogenicity on exposure to singlet oxygen. 1697 50

Mitochondria consume about 90 percent of oxygen used by the body, and are a particularly rich source of reactive oxygen species (ROS). In this research communication mitochondrial DNA (mtDNA) was isolated from fresh goat liver and modified in vitro by hydroxyl radical generated from UV irradiation (254 nm) of hydrogen peroxide. As a consequence of hydroxyl radical modification, mtDNA showed hyperchromicity and sensitivity to nuclease S1 digestion as compared to control mtDNA. Animals immunized with mtDNA and ROS-modified mtDNA induced antibodies as detected by direct binding and competition ELISA. The data suggest that immunogenicity of mtDNA got augmented after treatment with hydroxyl radical. IgG isolated from immune sera showed specificity for respective immunogen and cross-reaction with other nucleic acids. Binding of induced antibodies with array of antigens clearly indicates their polyspecific nature. Moreover, the polyspecificity exhibited by induced antibodies is unique in view of similar multiple antigen binding properties of naturally occurring anti-DNA antibodies derived from SLE patients.
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PMID:Immunogenicity of mitochondrial DNA modified by hydroxyl radical. 1771 39

CS1 (CD319, CRACC, SLAMF7, novel Ly9) activates NK cell-mediated cytotoxicity and proliferation of B lymphocytes during immune responses. The expression of CS1 is up regulated on B cells in multiple myeloma and systemic lupus erythematosus. In this study we describe the transcriptional regulation of mouse CS1 (mCS1) gene. We show that mCS1 gene transcription is regulated by YY1 (Ying Yang 1) and a unique (AG)n=36 DNA repeat element. YY1 is known to play a significant role in B cell development by regulating the pro B cell to pre B cell transition. The consensus DNA binding site for YY1 was detected using TRANSFAQ on the mCS1 promoter region. Mutations in the YY1 site led to a significant increase in mCS1 promoter activity indicating that YY1 represses mCS1 transcription. YY1 binds to the mCS1 promoter at the expected site in vivo and in vitro as tested by chromatin immunoprecipitation assays and super-shift EMSA assays respectively. Unique (CT)n=24 and (AG)n=36 DNA repeat elements are present on mCS1 promoter that are sensitive to S1 nuclease and engage in DNA triplex structure as confirmed by AFM (atomic force microscopy) imaging. Interestingly, the (AG)n=36 repeat element enhances mCS1 promoter activity.
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PMID:YY1 and a unique DNA repeat element regulates the transcription of mouse CS1 (CD319, SLAMF7) gene. 2331 24


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