Faculty Bibliography

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.

Background/Purpose: Psoriatic Arthritis (PsA) is linked to both obesity and an increased cardiovascular risk. However, the relationship between PsA disease activity and lipids, a major cardiovascular risk factor, has not been well studied. We assessed the relationship between PsA disease activity and lipid profiles in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. Methods: We performed a cross-sectional analysis of all CORRONA participants followed from 6/2008 to 10/2012 with complete data for lipids and disease activity. Longitudinal subanalysis of PsA patients with paired lipid measurements on stable statin doses was also performed. Moderate to high disease activity was defined as CDAI>10 and/or presence of enthesitis/dactylitis. Abnormal lipids were defined as: total cholesterol (TC) >200 mg/dl (5.17 mmol/L), High Density Lipoprotein (HDL)<40 mg/dl (1.0 mmol/L, men), HDL<50 mg/dl (1.3 mmol/L, women), Low Density Lipoprotein (LDL) >100 mg/dl (2.59 mmol/L), Triglycerides (TG) >150 mg/dl (1.7 mmol/L), and atherogenic ratio (TC/HDL) >5. Models were adjusted for gender, duration of PsA, mHAQ, disease-related medication use, smoking, body mass index (BMI), diabetes (DM), use of cholesterol lowering medications and fish oil. Results: Of 5713 PsA patients, 725 had complete data for lipids and disease activity. 284/725 (39%) had moderate to high disease activity. Compared to the low disease activity group, the moderate to high disease activity group had more women (57% vs 46%, p=0.006) and smokers (12.7% vs 7.7%, p=0.029), and had shorter disease duration (mean 8.7 vs 11.2 years, p=0.001). Moderate to high disease activity patients were more likely to be prescribed prednisone (13% vs 4.5%, p<0.001) and non-biologic DMARDs (63% vs 51%, p=0.002), but were less likely to be prescribed anti-TNFs (57% vs 66%, p=0.015). Mean BMI in the moderate to high and low groups were 31.7kg/m² and 30.6kg/m², respectively, p=0.02. There were no differences between !