Immunochemical studies on catechol-estrogen modified plasmid: possible role in rheumatoid arthritis.
ABSTRACT Increased concentrations of estrogen metabolites (catecholestrogens) have been found in rheumatoid arthritis (RA) but the exact patho-etiology remains elusive.
The binding of antibodies from the sera of RA patients and control subjects to native and modified DNA was studied by direct binding and inhibition ELISA, quantitative precipitin titration. Experimentally induced antibodies were also checked to detect oxidative lesions in the DNA as well as for the estimation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in different fluids of RA.
Anti-DNA IgG from RA sera, exhibited increased recognition of modified DNA than native DNA (nDNA; P < 0.001). The relative affinity of anti-DNA antibodies for modified and nDNA was in the order of 1.85 × 10(-7), 1.23 × 10(-7), and 1.2 × 10(-6). Samples of DNA from RA patients showed a significant inhibition in the induced antibody activity in comparison to DNA isolates from controls (P < 0.001). The concentration of 8-OHdG evaluated by induced antibody in RA patients was found to be significantly higher than controls ((P < 0.0001, P < 0.01, P < 0.05).
High binding of modified DNA with the IgG from RA patient might explain possible antigenic role of 4-OHE(2)-modified DNA in the production of anti-DNA antibodies. In addition, the induced antibodies have been shown to represent an alternative immunochemical probe to detect oxidative lesions in DNA as well as for the estimation of 8-OHdG levels in different body fluid of RA patients, which may be used as marker in the diagnosis of the disease.
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ABSTRACT: Endocrine-immune system interactions are the basis for predominance of autoimmune diseases in women with differences between the fertile and the postmenopausal periods. B cell-driven diseases reach the maximum incidence rate in the reproductive years, at least in women under the effects of serum estrogens and their metabolites (endocrine synthesis). On the other hand, the prevalent peripheral synthesis of estrogens, especially in advanced ages (intracrine synthesis), through the action of aromatases, modulate the immune/inflammatory response in peripheral tissues similarly in both female and male patients (final common pathway). Interestingly, tissue injury that occurs during chronic immune/inflammatory reaction induces tissue repair and homeostatic responses including cell proliferation, growth factor production and angiogenesis that might facilitate cancer progression. The successful treatment of chronic immune/inflammatory diseases obtained by using medications initially developed for use in oncology, such as antiproliferative drugs, B-cell depleting monoclonal antibodies support the inflammation-cancer link.Expert Review of Clinical Immunology 12/2013; DOI:10.1586/1744666X.2014.863149 · 3.34 Impact Factor
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ABSTRACT: Estrogen metabolites have been implicated in rheumatoid arthritis (RA) and cancer, although the mechanism remains unestablished. Some estrogen metabolites, which are used for the assessment of cancer risk, play an important role in RA. The pathways by which malignancies associated with RA remain elusive. Possible mechanism involves enzymatic or nonenzymatic oxidation of estrogen into catecholestrogen metabolites through semiquinone and quinone redox cycle to produce free radicals that can cause DNA modifications. Modifications of DNA alter its immunogenicity and trigger various immune responses leading to elevated levels of cancer and RA antibodies. However, the role of different estrogen metabolites as a mediator of immune response cannot be ruled out in various immune-related diseases.09/2013; 2013:748178. DOI:10.1155/2013/748178
Saudi medical journal 12/2014; 35(12):1442-54. · 0.55 Impact Factor