Cell bound complement activation products alone and in combination with low serum complement C3 or C4 have superior diagnostic performance in systemic lupus erythematosus

Abstract

Abstract BACKGROUND Cell-bound complement activation products (CB-CAPs) are sensitive and specific diagnostic markers of systemic lupus erythematosus (SLE). We compared the performance of CB-CAPs to low serum complement C3 or C4 in distinguishing SLE from other rheumatic diseases and healthy individuals. METHODS Adult subjects (n=1200) were enrolled from multiple academic centers, including SLE (498), healthy individuals (252) and subjects with other rheumatic diseases (450). Erythrocyte bound C4d [EC4d] and B-Lymphocyte bound C4d [BC4d] were quantitated using flow cytometry. Serum C3 and C4 levels were determined using immunoturbidimetry. Measurements included sensitivity, specificity, area under the curve (AUC) of the receiver operating characteristic curve (ROC) and Youden Index, for each marker as well as combinations. RESULTS Abnormal CB-CAPs status yielded 62% sensitivity with 88% specificity in distinguishing SLE from the group with other diseases compared to low C3/C4 status − 38% sensitivity, 93% specificity. Youden index was 0.492±0.03 for CB-CAPs compared to 0.313±0.03 for low C3/C4 (p<0.01). AUC was higher with BC4d (0.72) than with EC4d (0.68; p<0.01), low C3 (0.62; p<0.01), low C4 (0.62; p<0.01) and low C3 and/or C4 levels (0.66; p<0.01). The cumulative complement scoring system yielded higher AUC (0.81). A score with greater than 1 complement abnormality yielded 45% sensitivity and 98% specificity. CONCLUSION Our data suggests that CB-CAPs have greater diagnostic performance than low serum complement C3/C4. The combination of these complement abnormalities in a composite complement score is superior in distinguishing SLE from other rheumatic diseases and healthy individuals.