Background/Purpose: To assess the association between cell bound complement activation products (CBCAPS) and measures of disease activity and quality of life in systemic lupus erythematosus (SLE).

Methods: SLE patients (1997 ACR classification criteria) with active disease as defined by an SLE disease activity 2000 index (SLEDAI 2K) ≥ 6 points or the presence of a 2004 British Isles Lupus Assessment Group (BILAG) index A or B score were eligible for enrollment. However, only those screened patients with elevated CBCAPS (e.g. erythrocyte C4d levels [EC4d] above 15 units) were permitted entry into the study. Clinical activity measures, consisting of a modified SLEDAI 2K (mSLEDAI 2K excludes complement and anti-dsDNA components) and a BILAG index score, and quality of life assessments (short-form 36 [SF-36]) were performed monthly for one year. Patients were also evaluated monthly for EC4d and erythrocyte C3d (EC3d), serum complement levels (C3/C4) and anti-dsDNA antibody concentrations at each visit. EC4d and EC3d levels were determined by flow cytometry, and the mean net fluorescence intensity (MFI) was log transformed for the analysis. Statistical analysis consisted of generalized linear mixed models with random intercept and fixed slopes. 

Results: 33 patients (mean age 35 years; 94% female) were evaluated monthly for a total of 303 study visits (median 10 visits per patient, range 3-13). Anti-dsDNA positivity was observed in 61% and low complement levels in 70% of the cohort. The average (SEM) baseline EC4d and EC3d levels were 54.0±21.6 and 15.6±10.0 Net MFI, respectively, and decreased to 28.8±4.4 and 4.2±0.8 net MFI at the last visit. Similarly, the average mSLEDAI 2K and composite BILAG score (A=12, B=8, C=1 point) were 6.8±0.8 and 15.7±1.8 points at baseline, respectively, and decreased to 2.8±0.8 and 8.5±1.3 points, at the last visit. Mean SF-36 scores ranged from 42 (general health) to 68 (role emotional) at baseline. Generalized linear mixed models showed that the number of monthly follow up visits was significantly associated with clinical improvement (decreased mSLEDAI 2K and BILAG scores; increased SF36 scores). As presented in the Table, decreases in EC3d levels and increases in C4 levels were associated with reductions in mSLEDAI 2K and BILAG index scores, whereas increases in C3 levels were associated with reductions in mSLEDAI 2K only. The analysis also revealed that decreasing EC4d and EC3d levels were associated with improving quality of life (p<0.05) in 6/8 domains of the SF-36. Changes in C4 were not significantly associated with changes in quality of life measures. Increased C3 was associated with lower quality of life in 2/8 domains of the SF-36 (physical function and role physical).

Conclusion: Our data reveal that EC4d and EC3d levels are associated with changes in disease activity and quality of life measures in SLE.

Table Mixed model estimates