Double-stranded DNA, autoantibodies

J2. Jacob, L., Viard, J. P., Allenet, B., Anin, M. F., Slama, F. B., etal., A monoclonal anti-double-stranded DNA autoantibody binds to a 94-kDa cell-surface protein on various cell types via nucleosomes or a DNA-histone complex. Proc. Natl. Acad. Sci. USA 86, 4669—4673 (1989). 

Zl. Zack, D. J., Stempniak, M., Wong, A. L., Taylor, C., andWeisbart, R. H., Mechanisms of cellular penetration and nuclear localization of an anti-double strand DNA autoantibody. J. Immunol. 157, 2082-2088 (1996). 

Nancey S, Blanvillain E, Parmentier B, Flourie B, Bayet C, Bienvenu J, Fabien N Infliximab treatment does not induce organ-specific or nonorgan-specific autoantibodies other than antinuclear and anti-double-stranded DNA autoantibodies in Crohn s disease, Inflamm Bowel Dis 2005,11 986-991... 

Injection site reactions characterized by mUd to moderate erythema, itching, burning, and/or pain occur in approximately one-third of patients but rarely necessitate drug discontinuation. The impact of etanercept on the host s response to new or chronic infections is not fully understood. Serious infections and sepsis, including fatalities, have been reported in patients treated with etanercept. Increased levels of autoantibodies, including antinuclear antibodies and anti-double-stranded DNA antibodies, have also been reported, but the clinical significance of this observation is unknown. 

Animal models of disease, whether naturally occurring or artificially induced, provide valuable insights into human disease and allow rigidly controlled studies that are not possible in humans. Probably the most intensively studied model of an immune complex disease is the spontaneous lupuslike disease that occurs in certain inbred strains of mice, especially the (NZB x NZW) F, hybrid. Its study has provided insights with respect to genetic predisposition (H25), the role of endogenous retroviruses (D8), the influence of sex hormones (R9), the identification of T suppressor cell abnormalities (T3), and the propensity to form certain autoantibodies, especially to double-stranded DNA (S36) and to the RNA-protein complex, Sm (E2). Though animal studies are not the subject of this review, we emphasize that the entire concept and framework by which we view immune complex disease in humans are based on initial observations in animals. 

Although patients treated with etanercept commonly develop new antinuclear antibodies or anti-double-stranded DNA antibodies, there were no reports of cutaneous or systemic lupus erythematosus in early clinical trials. However, since then, at least eight cases have been reported, including five patients with a lupus-like syndrome, two with acute discoid lupus, and one with subacute cutaneous lupus erythematosus (26-29). All were women and they developed their first symptoms 6 weeks to 14 months after the first injection of etanercept. Antinuclear and/or anti-DNA antibodies were positive in most of them. Etanercept was withdrawn in all patients with features of systemic lupus erythematosus, and the symptoms resolved within 2-8 weeks. The skin lesions also improved with local glucocorticoids, despite continued etanercept treatment in two patients with discoid lupus or subacute cutaneous lupus erythematosus. This suggests that etanercept-induced autoantibodies are sometimes associated with clinical autoimmune disease. 

After taking sodium aurothiomalate for 10 months (cumulative dose 550 mg) a 12-year-old girl with severe exudative polyarthritis developed pericarditis, high titers of antinuclear antibodies, and antibodies to native double-stranded DNA (70). After withdrawal her sjmiptoms rapidly disappeared and did not recur after a follow-up period of 5 years. The titers of autoantibodies fell to normal within 1 year. 

Autoantibodies and autoimmunity Infliximab may increase the risk of autoimmunity, but the presence of antibodies did not predict the risk of lupuslike syndrome. In trials, the incidence of infliximab-induced anti-double-stranded DNA antibodies ranged from 5 to 34% of patients, depending on the assay method... 

Antinuclear antibodies (by IIF). If antinuclear antibodies by IIF are positive, specificity of the antinuclear antibodies should be determined. Antinuclear antibody specificities associated with the development of systemic autoimmune diseases are autoantibodies against double-stranded DNA, nucleosomes, histones, Ro/SS-A, La/SS-B, U1-RNP, Sm, DNA-Topoisomerase I (Scl-70), centromere protein, and Jo-1. 

Double-stranded DNA (dsDNA). Main target of autoantibodies in patients with systemic lupus erythematosus. DsDNA autoantibody is a diagnostic marker and classification criterion of this disease. 

To explain the presence in LaP mutant mice of a lymphoproliferative disorder and of autoantibodies against double-stranded DNA and nucleoproteins, it has... 

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