Measurement of cell-bound complement activation products enhances diagnostic performance in systemic lupus erythematosus

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 64; no. 12; pp. 4040 - 4047
• Main Authors: Kalunian, Kenneth C., Chatham, W. Winn, Massarotti, Elena M., Reyes-Thomas, Joyce, Harris, Cole, Furie, Richard A., Chitkara, Puja, Putterman, Chaim, Gross, Rachel L., Somers, Emily C., Kirou, Kyriakos A., Ramsey-Goldman, Rosalind, Hsieh, Christine, Buyon, Jill P., Dervieux, Thierry, Weinstein, Arthur
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Anti-Idiotypic - blood; Antibodies, Antinuclear - blood; Autoimmune diseases; B-Lymphocytes - immunology; Biological and medical sciences; Biomarkers - blood; Blood Platelets - immunology; Case-Control Studies; Complement Activation - physiology; Complement C4b; Cross-Sectional Studies; Diseases of the osteoarticular system; DNA - immunology; Erythrocytes - immunology; Female; Humans; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - diagnosis; Male; Medical sciences; Middle Aged; Multivariate Analysis; Peptide Fragments - blood; Receptors, Complement - blood; Rheumatic diseases; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sensitivity and Specificity; Studies; Vimentin - blood; Performance evaluation; Immunopathology; Connective tissue disease; Skin disease; Systemic lupus erythematosus; Systemic disease; Rheumatology; Autoimmune disease; Activation; Diagnosis
• ISSN: 0004-3591; 2326-5191; 1529-0131; 1529-0131; 2326-5205
• DOI: 10.1002/art.34669

Objective 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). Methods 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. Results 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. Conclusion An assay panel combining anti‐dsDNA, ANA, anti‐MCV, EC4d, and BC4d is sensitive and specific for the diagnosis of SLE.