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)

In vitro studies were carried out to determine if reactive oxygen species modified DNA molecules are the preferred antigen for anti-DNA antibodies found in SLE sera. Reactive oxygen species were generated by 254 nm irradiation of hydrogen peroxide. Single stranded breaks, decrease in Tm and modification of adenine (21.7%) and thymine (48%) were the major effects observed on native DNA fragments of 300 bp in length. The ROS-modified DNA showed increased binding with naturally occurring anti-DNA autoantibodies as compared to unmodified DNA fragments. These results were substantiated by competition ELISA. Measurement of binding with DNA fragments of varying size revealed considerably increased binding as the fragment size increased from 50 bp to 800 bp. The relative affinity of anti-DNA IgG for ROS-modified and native DNA fragments of 300 bp were in the order of 6.26 x 10(-8) M and 4.07 x 10(-8) M, respectively.
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PMID:Reactive oxygen species modified DNA fragments of varying size are the preferred antigen for human anti-DNA autoantibodies. 128 55

Hydrogen peroxide in the presence of short wavelength UV light was able to induce alterations in native DNA fragments of 300 bp (ROS-DNA), thereby rendering it immunogenic in experimental animals. The specificity of induced antibodies was investigated by direct binding and competition ELISA. Inhibition studies revealed nearly 89% inhibition in the antibody binding by the immunogen and recognition of native B-, A- and allied conformations presented by various synthetic polynucleotides. Gel retardation assay reiterated the formation of immune complexes between induced antibodies and native and ROS-DNA fragments. It was observed that naturally occurring anti-DNA autoantibodies from systemic lupus erythematosus (SLE) sera recognize ROS-DNA. The comparison of the specificities of anti-DNA autoantibodies from 10 SLE patients showed a 20-50-fold preference for ROS-DNA over native DNA. These results demonstrate that anti-DNA antibodies can be induced by ROS-DNA, and that some of the autoimmune DNA binding antibodies found in SLE may result from response to reactive oxygen species.
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PMID:Polynucleotide specificity of anti-reactive oxygen species (ROS) DNA antibodies. 840 95

Ribonucleoprotein (RNP) particles isolated from fresh goat liver nuclei were exposed to hydroxyl radical which induced modification in the gross structure of RNP particles. To evaluate the effect of hydroxyl modification on the antigenic properties of RNP and possible role of ROS-RNP in the initiation and development of SLE, enzyme immunoassays were carried out. SLE sera having high titre anti-DNA antibodies showed enhanced binding to hydroxyl modified RNP particles in comparison to unmodified RNP particles. In competition assay none of the SLE sera or isolated IgG showed preference for ROS-modified RNP particles over native RNP particles. These studies suggest that anti-RNP autoantibodies observed in subpopulation of SLE patients are generated by some other intra-or extracellular mechanisms and hydroxyl radical has probably no direct role in the initiation of antibodies.
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PMID:Attenuated antigenicity of ribonucleoproteins modified by reactive oxygen species. 963 28

Hydroxyl radical, a prominent entity of reactive oxygen species, is known to modify cellular DNA and has been implicated in several human diseases. A previously described monoclonal antibody (Mab) against reactive oxygen species-modified DNA (ROS-DNA), which preferentially recognizes ROS-modified epitopes on DNA, was used in this study. The epsilon-amino groups of lysine of the Mab were modified to study the role of these residues in Mab binding to ROS-DNA. The results demonstrate that modification of lysyl residues paralleled loss in Mab binding to ROS-DNA to the extent of 73%, suggesting the probable role of these positively charged amino acid residues in the complementarily determining regions of the Mab. The Mab was also used as an immunochemical probe to detect oxidative DNA damage in vivo in SLE. The Mab distinctly recognized five DNA samples out of eight from SLE patients and gave maximum inhibitions of 57, 58, 63, 64 and 70% in inhibition assay, while not reacting with DNA from normal, healthy population which served as negative control. High recognition of DNA isolates from SLE patients by the Mab having preferential binding to ROS-modified epitopes indicates increased oxidative stress in these patients leading to DNA damage which may contribute to the induction of antibodies cross-reacting with native DNA (nDNA).
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PMID:Detection of oxidative DNA damage by a monoclonal antibody: role of lysyl residues in antigen binding. 969 3

The effect of the hydroxyl radical on polyguanylic acid [poly(G)] was investigated with regard to progressive increase of autoantibodies against it in systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Rabbits immunized with both native and ROS-poly(G) induced high titre antibodies. Immune IgG exhibited a high degree of specificity towards the immunogen, reiterated visually by a gel retardation assay. The induced antibodies showed a wide range of cross-reactivity with various synthetic polynucleotides exhibiting B-, A-, and allied conformations. The specificity of induced antibodies resembled the diverse binding characteristics of lupus anti-DNA autoantibodies. Moreover, sera from scleroderma patients showed binding to native and ROS-poly(G). SLE and PSS autoantibodies showed preferential recognition of ROS-poly(G) over native poly(G). These results demonstrate that the hydroxyl modified guanine residues in DNA and RNA can induce circulating SLE and PSS autoantibodies.
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PMID:Reactive oxygen species modified polyguanylic acid: immunogenicity and implications for systemic autoimmunity. 977 15

Hydroxyl radical, generated by UV irradiation of hydrogen peroxide caused damage to native calf thymus DNA leading to strand breaks, base modification and decrease in melting temperature. The ROS-DNA was highly immunogenic in goat. The antibody activity was inhibited to the extent of 89% with the immunogen as inhibitor. Antigenic specificity of anti-ROS-DNA antibodies by competition ELISA showed multiple cross-reactivity, recognizing B-, A- and allied conformations. The immune complex formation with native and ROS-DNA was substantiated by band shift assay. A striking observation, is the enhanced recognition of ROS-thymine and ROS-poly(dT) by the induced antibodies. These investigations suggest that ROS might be the plausible candidate for the presentation of unique epitopes on ROS-DNA, in particular of thymine, inducing antibodies cross-reacting with native DNA and play an important role in the pathogenesis of SLE.
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PMID:Antigen binding characteristics of experimentally-induced antibodies against hydroxyl radical modified native DNA. 1005 81

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

The effect of hydroxyl radicals on polyinosinic acid [poly(I)] was studied. Strand breaks, base alteration and a decrease in absorbance at 248 nm (lambda max) were observed upon *OH modification of poly(I). The broad antigen specificity of the induced anti-poly(I) and anti-ROS-poly(I) antibodies showed diverse antigen binding characteristics similar to those of SLE autoantibodies. Recognition of both poly(I) and ROS-poly(I) by human SLE anti-DNA autoantibodies was observed. The possible significance of these findings in the etiology of SLE has been discussed.
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PMID:Antigenicity of poly(I) and ROS-poly(I) and their recognition of human anti-DNA autoantibodies. 1177 84

The hydroxyl radical generated by UV irradiation of hydrogen peroxide cause an extensive damage to guanine residues of ribohomopolymer, polyguanylic acid, poly (G) as investigated by spectrophotometric measurements, agarose gel electrophoresis, Sephadex G-200 gel filtration and DEAE Sephadex A-25 column chromatography. Native and ROS-poly (G) were highly immunogenic inducing high titre antibodies in rabbits. The antibodies showed wide range of cross reactivity with various synthetic polynucleotides exhibiting B-, A-, and allied conformations. The diverse antigen binding characteristics of the induced antibodies resembles to those of naturally occurring lupus anti-DNA autoantibodies. Sera from various SLE patients showed preferential binding to ROS-poly (G) than native poly (G), indicating that oxidatively modified guanine residues are better recognised. The significance of these findings in the induction of SLE anti-DNA autoantibodies by oxygen free radicals modified guanine residues in DNA has been discussed.
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PMID:Hydroxyl radical modification of polyguanylic acid: role of modified guanine in circulating SLE anti-DNA autoantibodies. 1291 8

Activation, proliferation and programmed cell death of immune cells are dependent on controlled production of ROS (reactive oxygen species). However, under chronic inflammatory conditions, large amounts of ROS generated are a major cause of many human degenerative diseases. ROS are known to cause DNA damage, leading to strand breaks, base damage and conformational changes. (1)O(2) (singlet oxygen), being one of the most potent ROS, is known to selectively react with the deoxyguanosine moiety in DNA. The effect of (1)O(2), generated by UV irradiation of Methylene Blue, on plasmid DNA was studied by UV spectroscopy and electrophoresis. The antibodies raised against the modified DNA in experimental animals induced a high titre. IgG was purified on a Protein A-Sepharose matrix, and oxidative lesions in DNA of SLE (systemic lupus erythematosus) and cancer patients were probed using anti-((1)O(2)-plasmid DNA) [anti-((1)O(2)-modified plasmid DNA)]. The DNA isolated from the sera of SLE and cancer patients was found to inhibit anti-(1)O(2)-plasmid DNA IgG activity, reiterating the results obtained with serum samples. These binding results indicate the presence of oxidative lesions in the SLE and cancer patients' genome caused by excessive production of ROS. The results confirm the damaging effect ROS has on DNA. The excessive production of reactive oxygen intermediates may be one of the factors responsible for the induction of autoimmune response seen in SLE and cancer.
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PMID:Immunogenicity of DNA modified by singlet oxygen: implications in systemic lupus erythematosus and cancer. 1693 12


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