Immunochemical studies on catechol-estrogen modified plasmid: possible role in rheumatoid arthritis.
BACKGROUND
Increased concentrations of estrogen metabolites (catecholestrogens) have been found in rheumatoid arthritis (RA) but the exact patho-etiology remains elusive.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Khan
Wahid Ali
WA
Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia. wahidalikhan@rediffmail.com
Moinuddin
Assiri
Abdullah S
AS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000209:etiology* / Q000276:immunology; D015415:Biomarkers; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry
D000974:Antibodies, Antinuclear; D015415:Biomarkers; D002393:Estrogens, Catechol; D004958:Estradiol; D000080242:8-Hydroxy-2'-Deoxyguanosine; C014036:4-hydroxyestradiol; D003849:Deoxyguanosine
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