Know Your Labs

Because of these considerations, there should be economic savings in employing a solid-phase immunoassay for quantitating an ANA. Thus, in an attempt to develop solid-phase ANA immunoassays, a number of groups have put onto the solid phase whatever antigens are typically assayed in the more specific ANA immunoassays (e.g., DNA, Sm, RNP, Ro/SSA, La/SSB, nucleoprotein, cell extracts, etc.). In published reports, the correlation coefficient between ANA titers and these solid-phase assays is quite good. Thus, many commercial firms have switched their ANAs to these solid-phase immunoassays.^4-23 Of concern, however, is the high frequency/percentage of false-negative results in patients with known SLE and related diseases, as well as the continued high frequency of “false positives” (e.g., a positive ANA in someone without SLE) in these studies.^15-21 Further work is needed to improve the sensitivity and especially the specificity of these solid-phase immunoassays to ensure that patients with SLE and related diseases are not missed by these solid-phase immunoassays.

Antibodies to DNA

Antibodies to DNA can be primarily divided into those that react with single-stranded (ss) DNA and those recognizing dsDNA.^24-26

Anti-ssDNA antibodies have been reported in SLE, rheumatoid arthritis, drug-related lupus, healthy relatives of patients with SLE, and, less commonly, in other rheumatic diseases. (See Table 2, p. 17.) Thus, anti-ssDNA has limited usefulness for the diagnosis of SLE or other rheumatic diseases. Anti-ssDNA does not correlate well with disease activity and are therefore not useful for disease management.

Antibodies to dsDNA are most frequently detected by solid-phase immunoassays, but also in some labs by the crithidia IF assay or occasionally the Farr radioimmunoassay. Most hospital and commercial labs do only one. The Farr assay probably has the highest specificity, and lowest sensitivity of the three assays for the diagnosis of SLE, while solid-phase assays have the highest sensitivity and lowest specificity; the crithidia assay falls in between. The Farr assay also has the disadvantage of using radioactive material, which most labs shun, and the crithidia test is very labor intensive. I prefer the ELISA assay for everyday use.

Anti-dsDNA are specific (95%) though not highly sensitive (70%) for SLE, making them very useful for diagnosis when positive.⁹ (See Table 2, p. 17.) They are occasionally found in other conditions, including rheumatoid arthritis, juvenile arthritis, drug-induced lupus, autoimmune hepatitis, and even in normal persons.

Titers of anti-dsDNA antibodies often fluctuate with disease activity, especially lupus nephritis, and are therefore useful in many patients for following the course of SLE. If a patient has a rising titer, or very high titer, but clinically is quiescent, I do not treat the serological abnormality, but consider it a warning sign that the patient needs to be followed more closely and treated when something happens clinically to warrant a change in therapy. However, some investigators have treated these serological abnormalities (especially when associated with low complement levels) and have reported improved clinical outcomes. Conversely, I use a falling titer in someone who is getting better after a flare on treatment as a guide in reducing treatment (e.g., corticosteroids and/or immunosuppressives).