Drs. Kalunian, Furie, Putterman, Ramsey-Goldman, Buyon, and Weinstein have received honoraria for serving on the Exagen Diagnostics advisory board (less than $10,000 each).
Systemic Lupus Erythematosus
Measurement of cell-bound complement activation products enhances diagnostic performance in systemic lupus erythematosus
Article first published online: 28 NOV 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 12, pages 4040–4047, December 2012
How to Cite
Kalunian, K. C., Chatham, W. W., Massarotti, E. M., Reyes-Thomas, J., Harris, C., Furie, R. A., Chitkara, P., Putterman, C., Gross, R. L., Somers, E. C., Kirou, K. A., Ramsey-Goldman, R., Hsieh, C., Buyon, J. P., Dervieux, T. and Weinstein, A. (2012), Measurement of cell-bound complement activation products enhances diagnostic performance in systemic lupus erythematosus. Arthritis & Rheumatism, 64: 4040–4047. doi: 10.1002/art.34669
- Issue published online: 28 NOV 2012
- Article first published online: 28 NOV 2012
- Accepted manuscript online: 29 AUG 2012 03:08PM EST
- Manuscript Accepted: 7 AUG 2012
- Manuscript Received: 2 MAY 2012
- Exagen Diagnostics
To determine the value of cell-bound complement activation products in combination with antinuclear antibody (ANA), anti–double-stranded DNA antibody (anti-dsDNA), and anti–mutated citrullinated vimentin antibody (anti-MCV) for the diagnosis of systemic lupus erythematosus (SLE).
This was a multicenter cross-sectional study in which 593 subjects were enrolled (210 SLE patients, 178 patients with other rheumatic diseases, and 205 healthy subjects). Complement receptor 1 levels on erythrocytes (ECR1) together with complement C4d levels on erythrocytes (EC4d), platelets (PC4d), and B cells (BC4d) were determined using fluorescence-activated cell sorting. Serologic markers were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed using area under the curve (AUC), logistic regression, and calculations of diagnostic sensitivity and specificity.
Anti-dsDNA was an insensitive (30%) but specific (>95%) marker for SLE. Levels of EC4d, BC4d, and PC4d were several times higher, and levels of ECR1 lower, in SLE patients compared to patients with other rheumatic diseases and healthy subjects. Among 523 anti-dsDNA–negative subjects, multivariate logistic regression analysis revealed that SLE was associated with ANA positivity (≥20 units), anti-MCV negativity (≤70 units), and elevated levels of both EC4d and BC4d (AUC 0.918, P < 0.001). A positive index score corresponding to the weighted sum of these 4 markers correctly categorized 72% of SLE patients. Specificity in relation to patients with other rheumatic diseases and healthy controls was >90%. The combination of anti-dsDNA and index score positivity yielded 80% sensitivity for SLE and 87% specificity against other rheumatic diseases.
An assay panel combining anti-dsDNA, ANA, anti-MCV, EC4d, and BC4d is sensitive and specific for the diagnosis of SLE.