Peter H. Schur

OBJECTIVE: To standardize outcome measures in systemic lupus erythematosus (SLE). Three indices were identified which could adequately describe outcome (disease activity, damage from disease, and health status); we describe here the development of the Disease Activity Index. METHODS: Twenty-four variables were identified as important factors in a disease activity index. These were used to generate 574 patient profiles, which were rated on a disease activity scale of 0-10 by 14 rheumatologists. A second rating of 10 of the profiles yielded scores that were not significantly different from the first, indicating that experienced clinicians can reliably make global estimates of disease activity. Multiple regression models were used to estimate the relative importance of the 24 clinical variables in the physicians' global rating of disease activity. These were estimated on a "training set" of 75% of physicians' ratings, and then validated on a "testing set," consisting of the remaining 25% of physicians' ratings. RESULTS: The explanatory power of the models in the training set was high (R2 = 0.93). The models' regression coefficients for the organ systems were simplified for easier use in clinical practice. This generated a "weighted" index of 9 organ systems for disease activity in SLE, the SLEDAI, as follows: 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic. The maximum theoretical score is 105, but in practice, few patients have scores greater than 45. The SLEDAI predicted well the physicians' ratings in the testing set (Pearson's correlation coefficients = 0.64-0.79). CONCLUSION: The SLEDAI is a validated model of experienced clinicians' global assessments of disease activity in lupus. It represents the consensus of a group of experts in the field of lupus research.

Antibodies were eluted from the isolated glomeruli prepared from the kidneys of 10 patients with the nephritis of systemic lupus erythematosus. Antibodies reacting primarily with buffer extracts of nuclei were eluted by acid treatment, and antibodies reacting mainly with DNA and nucleoprotein were eluted with deoxyribonuclease. Quantitative immunochemical studies revealed a high concentration of antinuclear antibody per milligram of gamma-globulin in glomerular eluates compared with that in the corresponding serums. The gamma-globulin of two eluates was found to consist predominantly of antinucleoprotein antibody. The selective elution of antinuclear antibodies was also indicated by the absence of other serum antibodies in the eluates. DNA antigen was demonstrated in the glomeruli of two kidneys with nephritis by means of isolated anti-DNA antibody labeled with fluorescein. In one of these cases, anti-DNA antibodies were also found concentrated in the glomeruli and, in the second, circulating anti-DNA antibodies were demonstrated in the patient's serum. The immunochemical evidence for the high specific activity of antinuclear antibodies and the association of DNA antigen with DNA antibody in glomeruli add further support for the antigen-antibody complex hypothesis for renal injury in systemic lupus erythematosus.

Six systems for defining and evaluating disease activity in patients with systemic lupus erythematosus (SLE) (the Ropes system, the National Institutes of Health [NIH] system, the New York Hospital for Special Surgery system, the British Isles Lupus Assessment Group [BILAG] scale, the University of Toronto SLE Disease Activity Index [SLE-DAI], and the Systemic Lupus Activity Measure [SLAM]) were tested on 25 SLE patients who were selected to represent a range of disease activity. The patients were evaluated independently by 2 physicians on 2 occasions approximately 1 month apart. Differences between patients demonstrated the largest source of variation in scores, accounting for 56-84% of the total variance, depending on the instrument. Differences between physicians (i.e., error) showed the next largest variation, 11-28% of the total variance, and differences between visits made up 5-16% of the total. The BILAG, SLE-DAI, and SLAM had the best inter-visit and inter-rater reliability. Convergent validity was shown by the strong correlations of scores among the different instruments (r = 0.81-0.97). All instruments correlated highly with the physicians' clinical impression of disease but less well with their evaluation of disease severity. The number of American Rheumatism Association criteria for SLE that were met by the patients correlated poorly with the physicians' global evaluation and with the scores of the instruments. The patients' self-reported disease activity scores correlated highly with the physicians' assessments of disease activity (r = 0.85-0.91), and the mean values from self-reports and from physicians' assessments were nearly equal. In contrast, severity scores correlated less well between self-reports and physician assessments (r = 0.49-0.69), and mean self-reported severity values were lower than the means from physicians. The BILAG, SLE-DAI, and SLAM systems appear to have better psychometric properties than the others for clinical research.

To clarify the association between certain immunologic factors and clinical activity in patients with systemic lupus erythematosus, 96 patients were studied. Those with antibodies to deoxyribonucleic acid (DNA) or heat-denatured DNA, or with serum complement levels of less than 50 C′H50 units per ml, were more likely to have renal involvement. Very low complement levels and high titers of complement-fixing antibodies to DNA were always associated with active disease, especially active renal disease, whereas the absence of these abnormalities usually indicated inactive renal disease. A 50 per cent fall in serum complement levels in 22 patients was accompanied by, or preceded the onset of, active nephritis in 19 patients. These serologic factors may thus reflect the in vivo formation of immune complexes that cause nephritis. Serial immunochemical observations may be useful in the management of patients with systemic lupus erythematosus.