Binding of SLE Autoantibodies to Native poly(I), ROS-poly(I) and Native DNA: A Comparative Study

Tasneem, Subia; Ali, Rashid

doi:10.1006/jaut.2001.0546

Cited by 12 publications

(4 citation statements)

References 43 publications

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“…Supplemented with vitamin E, the oxidised oil diet apparently decreased thiobarbituric acid reactive substance values in the kidney and spleen in this study. The hydroxyl radical-modified nucleic acids, such as RNA and DNA, might be agents for the induction of circulating SLE anti-DNA autoantibodies (Tasneem & Ali, 2001). Supplementation with vitamin C, vitamin E and b-carotene in human lymphocyte significantly decreased the DNA endogenous oxidative base and increased resistance to oxidative damage when challenged in vitro with H 2 O 2 (Duthie et al 1996;Brennan et al 2000).…”

Section: Discussionmentioning

confidence: 99%

The effects of vitamin E supplementation on autoimmune-prone New Zealand black × New Zealand white F1 mice fed an oxidised oil diet

Hsieh

Lin

2005

Br J Nutr

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The purpose of the present study was to investigate the effect of vitamin E supplementation on autoimmune disease in New Zealand black £ New Zealand white F 1 (NZB/W F 1 ) female mice fed an oxidised oil diet. First, 5-month-old mice were fed an AIN-76 diet containing either 150 g fresh soyabean oil/kg (15S), 50 g fresh soyabean oil/kg + 100 g oxidised frying oil/kg (5S10F) or 5S10F supplemented with all-rac-a-tocopheryl acetate at 275 mg/kg diet level (5S10F5E) or 550 mg/kg (5S10F10E), respectively, in experiment 1. The results showed that mice fed the 5S10F10E diet had a lower anti-double-stranded DNA IgG antibody level and a longer lifespan than those fed the 15S and 5S10F diets. Therefore, the 5S10F and 5S10F10E treatments were repeated in experiment 2 for further analysis. The results showed that vitamin E supplementation in the oxidised oil significantly decreased thiobarbituric acid-reactive substance values in the kidney and spleen of NZB/W F 1 mice. Interferon-g and IL-6 production by mitogen-stimulated splenocytes decreased in mice fed the 5S10F10E diet, whereas the secretion of IL-2 and IL-10 was not affected. The percentage of T-cells was significantly higher and that of MHC class IIbearing cells was lower in the spleens of the 5S10F10E group. The 5S10F10E group had a significantly higher linoleic acid (18 : 2n-6) composition than the 5S10F diet group. Therefore, vitamin E supplementation in oxidised oil might decrease oxidative stress, anti-double-stranded DNA IgG antibody, regulate cytokines and lymphocyte subsets, and subsequently alleviate the severity of autoimmune disease such as systemic lupus erythematosus under oxidative stress.

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Section: Discussionmentioning

confidence: 99%

The effects of vitamin E supplementation on autoimmune-prone New Zealand black × New Zealand white F1 mice fed an oxidised oil diet

Hsieh

Lin

2005

Br J Nutr

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“…It has been postulated that immune response against host antigens could result from genetic predisposition, exaggerated random B cell activity, cross‐reactivity between foreign and host antigens. The foreign antigens arise as a consequence of infection, inflammation, drug administration, environmental factors, free radicals [29–35] and scores of other modifying agents. ROS have gained considerable interest in recent years as plausible causative agents in the pathogenesis of several human degenerative diseases [36].…”

Section: Systemic Autoimmune Disordersmentioning

confidence: 99%

Oxygen free radicals and systemic autoimmunity

Ahsan¹,

Ali²,

Ali

2003

Clinical and Experimental Immunology

219

144

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SUMMARYReactive oxygen species generated during various metabolic and biochemical reactions have multifarious effects that include oxidative damage to DNA leading to various human degenerative and autoimmune diseases. The highly reactive hydroxy radical (·OH) can interact with chromatin and result in a wide range of sugar and base-derived products, DNA-protein cross-links and strand breaks. Studies from our laboratory have demonstrated that after modification the DNA becomes highly immunogenic and the induced antibodies exhibit variable antigen-binding characteristics. Systemic lupus erythematosus, a prototype autoimmune disease, is characterized by the presence of autoantibodies to multiple nuclear antigens. The detection of 8-hydroxyguanosine in the immune complex derived DNA of systemic lupus erythematosus patients reinforces the evidence that reactive oxygen species may be involved in its pathogenesis. Increased apoptosis and decreased clearance of apoptotic cells as observed in systemic lupus erythematosus (SLE) might well be a contributory factor in systemic autoimmunity. Clinically, titres of autoantibodies are closely related to the degree of renal inflammation. Anti-DNA antibodies may combine with circulating antigen and contribute to the deposition of immune complexes in renal glomeruli.

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“…The antigen-antibody interaction was visually detected by 1% agarose gel electrophoresis for 2 h at 30 mA followed by ethidium bromide staining and visualization under UV light [21]. A constant amount of antigen (1 lg) was incubated with increasing concentrations of IgG (0-80 lg) for 2 h at room temperature and overnight at 4°C to facilitate immune complex formation.…”

Section: Band Shift Assaymentioning

confidence: 99%

Oxidatively Damaged DNA: A Possible Antigenic Stimulus for Cancer Autoantibodies

Khan

Moinuddin

Alam

et al. 2010

Indian J Clin Biochem

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Reactive oxygen species (ROS) are cytotoxic at higher concentration resulting in cell death, mutations, chromosomal aberrations or carcinogenesis. In this study DNA was modified by singlet oxygen and superoxide anion radicals generated by illumination of riboflavin under 365 nm UV-light. The modified DNA induced high titre antibodies in experimental animals. In enzyme immunoassay, serum antibodies from cancer patients (n = 34) showed a higher recognition of the modified DNA, as compared to the native form. This was further confirmed by the gel-shift assay. Immune IgG were used as a probe to detect oxidative lesions in the DNA of cancer patients. DNA isolated from lymphocytes of cancer patients proved to be an appreciable inhibitor of the experimentally induced antibodies against the ROS-DNA. This indicates the presence of oxidative lesions in the DNA obtained from cancer patients. The results show that ROS induced oxidative damage to DNA in cancer patients generate neo-epitopes that are alien for the immune system, resulting in autoantibody formation.

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Binding of SLE Autoantibodies to Native poly(I), ROS-poly(I) and Native DNA: A Comparative Study

Cited by 12 publications

References 43 publications

The effects of vitamin E supplementation on autoimmune-prone New Zealand black × New Zealand white F1 mice fed an oxidised oil diet

The effects of vitamin E supplementation on autoimmune-prone New Zealand black × New Zealand white F1 mice fed an oxidised oil diet

Oxygen free radicals and systemic autoimmunity

Oxidatively Damaged DNA: A Possible Antigenic Stimulus for Cancer Autoantibodies

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