A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus

OBJECTIVE: To determine the degree to which changes in C3 and C4 precede or coincide with changes in systemic lupus erythematosus (SLE) activity, as measured by 5 global activity indices, the physician's global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLAM), and the modified British Isles Lupus Assessment Group (M-BILAG), and to evaluate the association between changes in C3 and C4 levels and SLE activity in individual organ systems. METHODS: Fifty-three lupus patients were observed monthly for 1 year in a longitudinal study. Lupus disease activity and complement levels were measured at each visit. Lupus flare was defined as a 1.0 (or greater) increase in the PGA, a 3-point increase in the M-SLEDAI, a 0.1 increase in the M-LAI, a 3-point increase in the SLAM, or a 4-point increase in the M-BILAG within a 1-month period. Flare rates were calculated for subgroups defined by previous (1 month before) or concurrent changes in complement levels. Logistic regression models were used to determine the significance of the association between recent changes in complement levels and flare, controlling for prednisone dosage. Similar models were used to assess the association between changes in C3 or C4 levels and increased SLE activity in specific organ systems. RESULTS: Lupus flares occurred at 12% of visits based on the PGA, 19% based on the M-SLEDAI, 25% based on the M-LAI, 13% based on the SLAM, and 12% based on the M-BILAG. Recent changes in C3 and C4 levels were not associated with flares based on 3 of the 5 activity indices. Flares defined by the M-LAI were more frequent when there was a concurrent decrease in C3 (odds ratio OR 1.9, 95% confidence interval 95% CI 1.1-3.1) or C4 (OR 2.1, 95% CI 1.3-3.6). Higher flare rates, as defined by the SLAM, were associated with previous increases in C3 (OR 1.6, 95% CI 1.0-2.6) and C4 (OR 2.2, 95% CI 1.2-3.9). When individual organ systems were analyzed, decreases in C3 and C4 were associated with a concurrent increase in renal disease activity (OR 2.2, 95% CI 1.4-3.5 and OR 1.9, 95% CI 1.1-3.4, respectively). Decreases in C3 were also associated with concurrent decreases in the hematocrit (OR 4.6, 95% CI 1.7-12.3), platelet (OR 2.5, 95% CI 1.5-4.1), and white blood cell (OR 2.2, 95% CI 1.3-3.6) counts. Previous increases in C3 levels were associated with a decrease in platelets (OR 1.7, 95% CI 1.1-2.7). A decrease in C4 was associated with a concurrent decrease in the hematocrit level (OR 3.2, 95% CI 1.3-7.5) and platelet count (OR 1.6, 95% CI 1.0-2.5). CONCLUSION: Decreases in complement levels were not consistently associated with SLE flares, as defined by global measures of disease activity. However, decreasing complement was associated with a concurrent increase in renal and hematologic SLE activity.