PT - JOURNAL ARTICLE AU - Chaim Putterman AU - Richard Furie AU - Rosalind Ramsey-Goldman AU - Anca Askanase AU - Jill Buyon AU - Kenneth Kalunian AU - W Winn Chatham AU - Elena Massarotti AU - Kyriakos Kirou AU - Nicole Jordan AU - Irene Blanco AU - Arthur Weinstein AU - Puja Chitkara AU - Susan Manzi AU - Joseph Ahearn AU - Tyler O'Malley AU - John Conklin AU - Claudia Ibarra AU - Derren Barken AU - Thierry Dervieux TI - Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements AID - 10.1136/lupus-2014-000056 DP - 2014 Oct 01 TA - Lupus Science & Medicine PG - e000056 VI - 1 IP - 1 4099 - http://lupus.bmj.com/content/1/1/e000056.short 4100 - http://lupus.bmj.com/content/1/1/e000056.full AB - 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.