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)

Little is known about endogenous systemic lupus erythematosus (SLE) plasma DNA even though it is the presumed precursor of DNA-containing immune complexes, thought to play a central role in lupus glomerulonephritis. DNA purified from SLE plasma formed discrete bands, corresponding to sizes of about 150-200, 400, 600, and 800 bp, closely resembling the characteristic 200 bp "ladder" found with oligonucleosomal (ON) DNA. By radiolabeling DNA while in whole plasma, the very small amounts present could be further characterized. All of 24 such specimens formed two or more discrete bands on 6% PAGE. Detergent treatment of plasma resulted in a DNA migration pattern similar to that of purified DNA, suggesting disruption of DNA-protein complexes. DNA purified from authentic ON and detergent-treated ON behaved similarly. A significant portion of DNA, labeled in SLE plasma could be specifically immunoprecipitated with monoclonal antihistone antibody as was the case with ON. These immunoprecipitates, when redissolved, exhibited the expected size distribution upon PAGE. It is concluded that DNA in SLE plasma occurs as a series of multimeric complexes, at least a portion of which is noncovalently bound to histone. These results are consistent with an ON-like structure for SLE plasma DNA as had been suggested by theoretical considerations and may have important implications for its immunologic behavior in SLE and perhaps other disorders.
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PMID:Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone. 236 27

The H1 histones represent the most heterogenous class of histone proteins. In this study, we analyzed the specificity of human antibodies against 6 H1 subtypes. H1 histones from rat organs were separated by reverse-phase high performance liquid chromatography and used as antigens in immunoblotting experiments. Sera containing anti-histone H1 antibodies were obtained from patients with systemic lupus erythematosus. Of the 9 sera tested, 2 reacted with only 1 H1 subtype. The other sera recognized different combinations of H1 subtypes. Only 1 serum reacted with all 6 H1 subtypes. Histones H1.5 and H1.1 were the subtypes most frequently recognized by the human autoantibodies. Our data indicate that human anti-H1 antibodies represent a heterogenous population, directed mainly against epitopes localized in the variable region of the H1 molecule.
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PMID:Autoantibodies against different histone H1 subtypes in systemic lupus erythematosus sera. 239 Jan 29

The sera of patients with systemic lupus erythematosus (SLE) and drug-induced lupus (DIL) were used to study the antigenic epitopes on nuclear histones that bind antibodies in these sera. ELISA and immunoblotting techniques showed that antibodies from both patient groups bound all classes of intact histone: H1 greater than H2B greater than H2A greater than H3 greater than H4. The different classes of histone were enzymatically or chemically cleaved to produce a series of peptide fragments which were then used to map the reactive epitopes by ELISA and immunoblotting. Ten of 11 DIL sera and 11 of 12 SLE sera bound the carboxy and amino terminal peptides. Only one sera of each group bound to the central hydrophobic polypeptide. The reactivity of DIL sera with fractionated histone polypeptides was similar to that observed with SLE sera. This observation suggests that the histone epitopes reacting with DIL sera are no less restricted than those reacting with SLE.
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PMID:Antibodies from patients with drug-induced and idiopathic lupus erythematosus react with epitopes restricted to the amino and carboxyl termini of histone. 241 12

Prolonged treatment with chlorpromazine is often associated with the development of antinuclear antibodies, an immunoglobulin M lupus anticoagulant, and polyclonal serum IgM elevation, but not with clinical features of systemic lupus erythematosus (SLE). Sera from 62 long-term psychiatric patients given treatment daily with 100 mg or more of chlorpromazine for at least 1 year were screened for antinuclear antibodies by indirect immunoperoxidase assay using HEp-2 cells. In 26 samples, antinuclear antibody titers greater than or equal to 1:40 with a homogeneous pattern were seen when anti-human IgM was used as the second antibody, three sera samples reacted with IgG, and four samples reacted with both IgG and IgM antisera. The antinuclear antibody antigenic reactivity was investigated by using histone and nonhistone nuclear antigens by enzyme-linked immunosorbent assay and passive hemagglutination techniques. Forty serum samples reacted with histone. Twenty-five samples reacted with deoxyribonucleoprotein (DNP), 28 with single-stranded DNA, and two with double-stranded DNA. No reaction was obtained with the extractable nuclear antigens RNP or Sm. These results indicate that chlorpromazine-induced antinuclear antibodies, like the antinuclear antibodies induced by hydralazine and procainamide, react mainly with histone nuclear antigens. Unlike the hydralazine and procainamide response, in which both IgG and IgM antibodies are demonstrated, the chlorpromazine-induced autoantibodies are predominantly of the IgM class.
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PMID:Characterization and antigenic specificity of chlorpromazine-induced antinuclear antibodies. 242 28

We have identified regions within core histones that are antigenic for autoantibodies in systemic lupus erythematosus (SLE) and drug-induced lupus. An immunoblotting technique was used to determine the reactivity of lupus antibodies for intact histones and for trypsin-resistant histone fragments that lack the amino- and carboxyl-terminal amino acids that are normally exposed in native nucleosomes. In SLE, the predominant anti-histone response was restricted to epitopes in the trypsin-sensitive regions. Of 20 SLE sera that had strong antibody activity for multiple intact histones, 17 showed minimal activity with any of the corresponding trypsin-resistant fragments. A markedly different pattern of reactivity was present in sera of patients with procainamide (Pr)-induced lupus in which antibodies to H2A, H2B, and the H2A-H2B complex had strong fragment activity. Interestingly, recognition of trypsin-resistant fragments was also noted in a small number of SLE sera that contained antibodies to the H2A-H2B complex. In contrast to both SLE and Pr-induced lupus, antibodies induced by hydralazine (Hy) reacted primarily with H3 and H4. Furthermore, these antibodies bound equally well to the corresponding trypsin-resistant regions that are thought to be relatively unexposed in native nucleosomes. Thus, the specificities of anti-histone antibodies in SLE, Pr-induced lupus, and Hy-induced lupus are markedly different, but in each disease reactivity appears to be restricted to a limited number of histone determinants. The data raise the possibility that autoantigen in the form of native nucleosomes may be recognized in SLE and possibly in Pr-induced lupus. In contrast, the propensity of Hy to induce autoantibodies to determinants usually not recognized in SLE or Pr-induced lupus may suggest a different immunogenic stimulus in this disease.
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PMID:Anti-histone antibodies in idiopathic and drug-induced lupus recognize distinct intrahistone regions. 243 24

Using the technique of immunoblotting, we assessed the ability of sera from 19 patients with drug-induced lupus to bind individual histones and specific histone fragments. The pattern of histone epitopes bound by sera from 9 patients with procainamide-induced lupus was very similar to that described previously in spontaneous systemic lupus erythematosus. In contrast, sera from 10 patients with hydralazine-induced lupus bound a broader array of individual histones and recognized a different set of histone epitopes. We conclude that these 2 drugs induce antihistone antibodies through somewhat different mechanisms, which possibly involve differences in their ability to structurally alter chromatin.
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PMID:Autoantigenic histone epitopes: a comparison between procainamide- and hydralazine-induced lupus. 244 Apr 52

Antihistone antibodies are prevalent in systemic lupus erythematosus (SLE) and are the predominant autoantibody in patients treated with various drugs. Total histones consist of 5 classes and various histone-histone and DNA-histone complexes. Antibody binding to these various potential antigens has been measured by solid phase and Western blot immunoassays. Relatively unique profiles tend to characterize disease groups, but SLE sera were heterogeneous, displaying reactivity with only 1 to all 5 histones. Antihistone antibodies from human sera as well as murine monoclonal antibodies showed the capacity to react with more than 1 histone class. However, the fine specificities of antihistone antibodies were often assay dependent. Explanations for these discrepancies include degraded and impure histone preparations, irreversible denaturation and the role of soluble histones in biological fluids.
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PMID:Antihistone antibodies in systemic lupus erythematosus. 244 Oct 43

Monoclonal anti-poly(ADP-ribose) (MRP-2) was primarily a product of a hybridoma selected by binding to poly(ADP-ribose) from an autoimmune MRL/Mp-lpr/lpr (MRL/1) mouse. Detailed examination revealed that anti-poly(ADP-ribose) monoclonal IgMK antibody bound not only to left-handed Z-DNA and single-stranded (ss) DNA but also to a conformational epitope formed by histone and double-stranded (ds) DNA. A reconstitution study revealed that association of dsDNA with histone H3 plus H4 was essential for their binding to MRP-2 monoclonal antibody. MRP-2 monoclonal antibody acted as a rheumatoid factor (RF). Since some monoclonal or polyclonal human serum antibodies of rheumatoid arthritis (RA) or mixed connective tissue disease (MCTD) have been reported to recognize shared epitopes of denatured IgG and DNA-histone (nucleosomes), this MRP-2 monoclonal antibody with the similar activity derived from a lupus-prone mouse will be useful for the studies on the etiology of autoantibodies associated with RA, MCTD and systemic lupus erythematosus (SLE).
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PMID:A unique monoclonal antibody derived from a lupus-prone mouse with multiple bindings to autoantigens associated with rheumatic disease. 246 46

An MRP-2 monoclonal antibody (MoAb) was primarily a product of hybridoma selected by binding to poly(ADP-ribose) from a lupus prone MRL/Mp-lpr/lpr (MRL/l) mouse, and was shown to cross-react with single-stranded (ss) DNA. Detailed examination revealed that MRP-2 MoAb bound to a conformational epitope formed between double-stranded (ds) DNA and total histone: both H3 and H4 were essential for the formation of this conformational epitope with dsDNA. Because of this characteristic of the MoAb, its ability to induce lupus erythematosus (LE) cells was examined in an indirect LE test with peripheral blood of MRL/Mp-+/+ (MRL/n) mice, which develop a mild form of lupus after the age of one year. MRP-2 MoAb was found to induce hematoxylin bodies, LE rosettes and LE cells, but a direct LE test using MRL/n mouse blood did not induce LE cell phenomena. This is the first demonstration of induction of LE cells by a MoAb that binds to dsDNA-histone complexes.
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PMID:Lupus erythematosus cell formation by a monoclonal antibody derived from an autoimmune MRL/Mp-lpr/lpr mouse. 246 47

Autoantibodies to defined cellular antigens in systemic lupus erythematosus (SLE) are usually directed to conserved epitopes on ubiquitous macromolecules including histone, Sm + nRNP (URNP particles), DNA, and La(SSB). We report here that the autoimmune response to the Ro(SSA) RNA protein particle is directed to epitopes on the human antigen which are not conserved in evolution. Ro(SSA) from bovine, rat, and mouse Ro(SSA) particles cross-react with human autoantibodies less effectively than does human Ro(SSA), and antigenically active Ro(SSA) is not detectable in chicken thymus extracts with the assays employed. These data suggest a special role for the Ro(SSA) antigen in the initiation and/or perpetuation of the anti-Ro(SSA) response in autoimmune disease.
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PMID:Autoimmune response to the Ro/SSA particle is directed to the human antigen. 247 59


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