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Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA
Chaim Putterman1, Richard Furie2, Rosalind Ramsey-Goldman3
1Albert Einstein College of Medicine and Montefiore Medical Center , Bronx, New York , USA.
Insights
Cell-bound complement activation products (CBCAPS) show higher sensitivity for diagnosing systemic lupus erythematosus (SLE) than traditional markers. Combining CBCAPS with other autoantibodies aids in differentiating SLE from other conditions.
Area of Science:
- Immunology
- Rheumatology
- Clinical Diagnostics
Background:
- Systemic lupus erythematosus (SLE) diagnosis relies on clinical and serological markers.
- Current serological tests for SLE, including anti-dsDNA and complement levels, have limitations in sensitivity and specificity.
- Cell-bound complement activation products (CBCAPS) represent a potential new diagnostic avenue.
Purpose of the Study:
- To compare the diagnostic performance of erythrocyte-bound (EC4d) and B cell-bound (BC4d) complement activation products (CBCAPS) against anti-dsDNA antibodies and complement C3/C4 in SLE.
- To evaluate the utility of CBCAPS in differentiating SLE from other rheumatic diseases and healthy individuals.
- To assess the correlation between CBCAPS, disease activity, and other serological markers in SLE patients.
Main Methods:
- A cohort of 794 subjects (304 SLE, 285 other rheumatic diseases, 205 controls) was analyzed.
- Anti-dsDNA antibodies were measured by solid-phase immunoassays.
- EC4d and BC4d were quantified using flow cytometry, and complement C3/C4 by immunoturbidimetry.
- Disease activity was assessed using the SELENA Modification of the Systemic Lupus Erythematosus Disease Activity Index.
- A combined methodology incorporating CBCAPS and other autoantibodies was developed and statistically analyzed using ROC curves.
Main Results:
- Both EC4d and BC4d demonstrated higher diagnostic accuracy (AUC) than C3 and C4 levels.
- BC4d showed significantly higher AUC than anti-dsDNA antibodies.
- A combined methodology using EC4d, BC4d, anti-dsDNA, and other autoantibodies achieved 80% sensitivity for SLE with high specificity across various control groups.
- Elevated CBCAPS, reduced complement, and anti-dsDNA were associated with higher SLE disease activity.
Conclusions:
- CBCAPS exhibit superior sensitivity compared to conventional complement and anti-dsDNA measurements for SLE diagnosis.
- The combination of CBCAPS with other autoantibodies offers a promising tool for the differential diagnosis of SLE.
- CBCAPS may improve diagnostic accuracy and aid in distinguishing SLE from other autoimmune conditions.
Objective:
To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE).
Methods:
The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity.
Results:
AUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03).
Conclusions:
CBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.
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