DNA is poorly immunogenic and the production of anti-dsDNA antibodies could be linked to the association of DNA with more immunogenic protein antigens (85). Cellular DNA is associated with proteins in nucleosomes and it now appears more appropriate to consider the anti-DNA antibody production as a response to a DNA-protein complex. Tests for DNA antibodies are less sensitive than that for ANA, but are more specific for SLE, particularly as these antibodies are rarely seen in normal individuals. Antibodies to dsDNA may be measured using immunodiffusion, complement fixation, RIA, a fluorescent assay for a DNA-containing organelle in the parasite Crithidia lucillae and ELISA. These antibodies are found in 50-90% of untreated patients with SLE and, apart from some cases of Sjögren's syndrome and chronic active hepatitis, they are virtually diagnostic for the disease. High titers of DNA antibodies are usually associated with renal disease and are often accompanied by low levels of serum complement activity, indicating the presence of circulating immune complexes (86, 87). No direct correlation between the levels of circulating anti-dsDNA antibodies and the DNA content of immune complexes was found (88). Clinical improvement in SLE is usually associated with a significant decline in or complete disappearance of DNA antibodies, accompanied by normalization of serum complement levels (89-91). Conversely, a rise in DNA antibodies in the presence of a decline in serum complement generally is associated with a high frequency of exacerbation of SLE nephritis. In clinical practice, the measurement of DNA antibodies is not only useful for the diagnosis but also for the monitoring of disease activity.
In future, the determination of antibodies against nucleosomes (=complexed DNA) may play an important role in SLE, since there is some evidence that nucleosomes are major autoantigens in human SLE and that antinucleosomal antibodies are highly specific for this disease (92). Whether the anti-nucleosome antibodies are a better tool than anti-dsDNA antibodies for diagnosing SLE has to be further investigated.
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Material
Pattern: n-DNA
Substrate: Crithidia luciliae
Description n-DNA positive sera show a staining fluorescence in the kinetoplast, showed by the nucleus and basal.
Method
Indirect immunoflourescence method. |
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