Correlation between levels of DNA antibodies and clinical disease activity in SLE.

Abstract

SUMMARY Sera were tested from 23 patients with systemic lupus erythematosus followed over a period of 1 to 5 years. Antibodies to native DNA were measured and correlated retrospectively with clinical evidence of disease activity. The overall degree of correlation between the presence of DNA antibodies and evidence of disease activity was good (P<0001). Of 206 sera tested, only 4 had a normal DNA antibody at a time when significant clinical activity was noted. In contrast, 34 sera had mild to moderately raised DNA antibody levels at times of clinical remission. Although DNA antibodies are a useful investigation in the monitoring of disease activity, changes in therapy should not necessarily be made on DNA antibody levels alone.Systemic lupus erythematosus (SLE), although a relatively uncommon disease, provides one of the best examples of an immune complex disease in man. An antigen of major importance in SLE is doublestranded native DNA (n-DNA), and the ability to measure antibody to n-DNA by various techniques has proved particularly useful in diagnosing and monitoring disease activity (Koffler et al., 1971;Koffler, 1974). This paper presents our evaluation of DNA antibody measurements in monitoring disease activity in 23 cases of SLE followed-up over a period of 1-5 years. Materials and methods206 sera from 23 cases who satisfy the ARA criteria for the classification of SLE were studied. All cases have been studied serially over at least one year. Serum samples were not taken more frequently than at 2-weekly intervals.Antibodies to n-DNA were measured using a millipore filter technique (Ginsberg and Keiser, 1973) and 3H labelled n-DNA extracted from a human amnion cell line (HAE 70) (Russell and Percy, 1974). Normal levels in our laboratory are 0-10% (<3-7 ,ug DNA bound/ml serum). This Accepted for publication July 8, 1976 Correspondence to Dr. P. Davis, Department of Medicine, 9-112 Clinical Sciences Building, University of Alberta, Edmonton, Alberta, Canada method using a uniform DNA gives reproducible results: 2 SD=4 9 %. Internal control is obtained by including three standard reference sera. The purity of the extracted DNA was checked using the following parameters. (1) Reduction in fluorescence with ethidium bromide at increased pH showed less than a 5% contamination with single-stranded chains or breaks (Morgan and Pulleybank, 1974 Hippel, 1975). (4) Single-stranded DNA was removed from the double-stranded DNA by millipore filter due to the affinity of singlestranded DNA for nitrocellulose (Riggs et al., 1970).Clinical evidence of disease activity was assessed by the presence of the following clinical signs or laboratory tests: active dermal manifestations, mouth ulcers, active hair loss, synovitis, pleurisy, pericarditis, urinary cellular casts, rising or persistently raised (>3 5 g/24 h) proteinuria, mental deterioration or recent neurological signs, myositis, thrombocytopenia, or persistent unexplained fever. Emphasis was placed on the presence of an actively changing clinical status rather than si...

Autoantibodies that bind glomeruli: Cross‐reactivity with bacterial antigen

“…Anti-doublestranded DNA (anti-dsDNA) antibodies are present in the serum of most SLE patients, and fluctuations in titers correlate with disease activity, especially glomerulonephritis (1,2). The association of nephritis with anti-DNA reactivity is strengthened by the demonstration that anti-DNA antibodies can be eluted from diseased kidneys (3,4).…”

“…Dr. Chowdhry's work was supported by a Fellowship from the New York Chapter of the Arthritis Foundation. 1 (16). Furthermore, only half of the Ig eluted from the kidneys of lupus patients binds to DNA (12,17,18).…”

C4a anaphylatoxin levels as an indicator of disease activity in systemic lupus erythematosus

“…Neither DNA antibody assays (Davis, Percy & Russell, 1977;Bresnihan, 1979) nor total complement levels (Valentijn et cd., 1985;Morrow et al, 1982) have proved sensitive enough to be individually reliable, whilst tests for circulating immune complexes have quite often failed to correlate with active disease (Abrasera/., 1980; Inman era/., 1980), a tendency supported by the distribution of Clq binding activity in the present study. Currently, the best approach to the investigational monitoring of patients with SLE is to carry out multiple laboratory measurements, even though such a combined approach does not reliably predict active or aggressive disease in all patients (Morrow et al, 1982).…”

Serologic markers of lupus nephritis in patients: use of a tissue-based ELISA and evidence for immunopathogenic heterogeneity

“…differences between groups 1 and 2 were not significant) [33]. It is also possible that the absence of detectable anti-dsDNA antibodies in nephritis is due to the lability of these antibodies to treatment [34], a decline in antibody titres just before onset of renal disease [35], the formation of immune complexes in circulation [7], or the concentration of low levels of antibody in the kidney [36]. Since our study was retrospective, many specimens were procured on treated patients or at the onset of renal disease (rather than before), and thus the relatively low incidence of antidsDNA antibodies in our cohort may reflect these problems.…”