SENSITIVITY AND SPECIFICITY OF PLASMA AND URINE COMPLEMENT SPLIT PRODUCTS AS INDICATORS OF LUPUS DISEASE-ACTIVITY

Objective. To determine if measurement of serum complement split produ cts (C4d, Bb, C5b-9) is better than conventional C3 and C4 measurement s in distinguishing patients with varying degrees of lupus disease act ivity, and to determine if the presence of C3d in urine is helpful in distinguishing lupus patients with from those without early lupus neph ritis. Methods. Lupus disease activity,vas prospectively determined at 3 consecutive visits an average of 4 months apart, using the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disea se Activity Index (SLEDAI), and physician global assessment (PGA). Blo od samples were evaluated for the presence of C4d, Bb, and C5b-9 by qu antitative microsassay plate enzyme immunoassay at each patient visit, We characterized urinary excretion of C3 fragments (with attention to C3d) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis wit h Western blotting. Results. Thirty-one SLE patients, were enrolled in the study, The mean SLAM score and the mean SLEDAI score each correla ted well with the PGA at all 3 visits, A SLAM score of 6 and a SLEDAI score of 4 had the best overall sensitivity and specificity for predic ting moderate-to-severe disease activity by PGA (100% and 73%, respect ively, for the SLAM and 86% and 94%, respectively, for the SLEDAI), Se rum C4d and Bb were more sensitive indicators of current moderate-to-s evere lupus disease activity at all 3 visits than were serum C5b-9, C3 , and C4. C3 and C4 were more specific indicators of moderate-to-sever e disease activity, Serum C4d and Bb were more sensitive at predicting moderate-to-severe disease activity at subsequent visits than were C5 b-9, C3, and C4. Urine C3d was better than C3, plasma C4d, Bb, C5b-9 a nd anti-double-stranded DNA antibody in distinguishing patients with f rom those without acute lupus nephritis (P = 0.02). Conclusion. C4d an d Bb are sensitive indicators of moderate-to-severe lupus disease acti vity and may be most helpful in situations where conventional measurem ents are not, such as in lupus patients whose C3 and C4 levels remain normal despite evidence of clinical disease activity, It appears from this study that detection of urine C3d may be a simple way of measurin g complement activation in the setting of lupus renal disease, The ava ilability of instruments for clinical disease activity measurement suc h as the SLAM and the SLEDAI may enable more consistent definition of lupus disease activity and may thus provide a means for better examini ng the role of complement activation products in predicting lupus dise ase activity In larger patient populations.