D A Isenberg

Measurement of anti-DNA antibodies: a reappraisal using five different methods.

One hundred and thirty coded sera, 60 from patients with systemic lupus erythematosus (SLE) and 70 from patients with other autoimmune rheumatic diseases were tested for deoxyribonucleic acid (DNA) binding activity by five different types of assay. These were enzyme linked immunosorbent assay (ELISA) (distinguishing IgG and IgM anti-ssDNA and anti-dsDNA), Crithidia luciliae, a nitrocellulose filter assay, the Amersham kit, and another modified Farr assay, the radioimmunoassay (RIA) (UK). The Crithidia test was the most specific, none of the controls was positive, but the least sensitive (13% positive only). The RIA (UK) was the most sensitive (57% positive). In most of the assays 3-9% of the controls were positive. When the SLE sera were analysed according to disease activity the IgG anti-dsDNA ELISA, all three RIA values, and the Crithidia test values were raised in all the patients with severely active disease. Some patients with inactive disease, however, were positive in each of the tests. The best interassay correlations (r less than 0.49) were found between RIA (UK), and ss IgG and the Amersham kit; and between ds IgG and ss IgG. In the main, however, it was clear that different assays are dependent upon distinctive properties of DNA antibodies. It seems inevitable that most major rheumatology units will require more than one anti-DNA antibody assay.

Disease activity in systemic lupus erythematosus related to a range of antibodies binding DNA and synthetic polynucleotides.

Antibodies to dDNA, nDNA, Z-DNA, poly(dT), poly(I), poly(dG.dC), poly(dA.dT), and total IgG and IgM were measured in five serial bleeds from 39 patients with systemic lupus erythematosus (SLE). The main findings were that those patients with renal disease form a distinct subset whose antibody levels correlate well with disease activity; anti-poly(dT) antibodies showed the best overall correlation with disease activity; and discriminant functional analysis demonstrated a major improvement in correlation of disease activity with combinations of antibodies to dDNA/nDNA/Z-DNA/poly(dT) (generally 50% or more were correctly classified) than with dDNA or nDNA alone (generally less than 25% correct). Serum IgG (but not IgM) correlated significantly (p less than 0.01) with six antibodies, suggesting that polyclonal activation plays a part in the development of these antibodies, though antibody cross reactivity is not excluded.

Disease specificity of antibodies to poly (ADP-ribose); their relationships to anti-DNA antibodies and to disease activity in lupus.

In this study we have measured the level of anti poly (ADP-ribose) antibodies in the sera of a number of patients with SLE and their relatives, patients with a wide variety of other autoimmune and infectious diseases, and a group of normal healthy controls. It was found that these antibodies were not disease specific but were present in nine out of thirteen groups tested in significant numbers. The levels of anti poly (ADP-ribose) antibodies and anti DNA antibodies in SLE patients bled serially were also measured. The level of these antibodies fluctuated in parallel in many of these patients, although the anti poly (ADP-ribose) antibodies reflected disease activity more accurately in some.