Clinical value of anti-ssDNA (denatured DNA) autoantibody test: beauty is in the eyes of the beholder

Abstract

The recent guidelines for the clinical use of antinuclear antibody tests issued by a Committee of the College of American Pathologists (CAP), suggest widespread misunderstanding of the clinical value of testing for the level of anti-ssDNA (single-stranded DNA or total DNA) IgG antibodies. This misunderstanding may stem from misconceptions about the manner in which clinicians use, in clinical context, immunoassays that have results expressed on a wide numerical scale. When the anti-ssDNA antibody (Ab) test is used for the differential diagnosis of new patients suspected of an inflammatory rheumatic disease the clinical sensitivity for systemic lupus erythematosus (SLE) is close to 100%, and the specificity about 85%. Since anti-dsDNA (double stranded DNA) is present in only about 65% of new SLE patients, an abnormal anti-ssDNA Ab test in the remaining 35% provides the clinician with a valuable clue to search for other criteria for SLE. Contrary to a widely held belief that anti-ss-DNA Ab occurs frequently in patients with rheumatoid arthritis (RA), anti-ssDNA is present only in 10–15% of this patient population and then at relatively low levels. There is evidence that anti-ssDNA, like anti-dsDNA, is involved in the pathogenesis of lupus nephritis. Moreover, the increase in anti-ssDNA Ab level appeared to be the best predictor of forthcoming increase in anti-dsDNA and SLE flare. In a context of symptoms different from those of rheumatic diseases, anti-ssDNA antibodies may be elevated in a relatively high proportion of patients with any of several diseases; leukemia, preeclampsia, chronic hepatitis, renal complications of diabetes, and some inflammatory neurological diseases. In conclusion, anti-ssDNA helps to rule out SLE, helps in the diagnosis of SLE when anti-dsDNA is not present and is useful in follow-up of SLE patients. Like most other quantifiable laboratory indicators of abnormality, anti-ssDNA Ab test is also useful in clinical context for the diagnosis and prognosis of several other condition.