Background/Purpose: We sought to evaluate the usefulness of cell bound complement activation products (C4d deposition on erythrocytes [EC4d] and platelets [PC4d]) in the monitoring of disease improvement in systemic lupus erythematosus (SLE).

Methods: 58 patients with SLE from the Oklahoma Lupus Cohort were evaluated at two visits (baseline and follow-up) with the stipulation that there must be at least mild/moderate disease activity, in the clinician’s opinion, at the first visit. Standard of care treatments were given. Clinical assessments included the Systemic Lupus Erythematosus Disease Activity Index without the complement and anti-dsDNA descriptors (non serologic SLEDAI or ns-SLEDAI) and the British Isles Lupus Assessment Group (BILAG 2004) index. Serum C3 and C4 levels were measured with nephelometry. EC4d and PC4d were determined using flow cytometry (expressed as mean fluorescence intensity [MFI], and natural log transformed). Statistical analysis included linear regression, and multivariate linear mixed effect models using a random intercept and fixed slope.

 Results: At baseline, mean ns-SLEDAI score was 6.4±0.4 while the cumulative BILAG multiorgan score was 10.3±0.9. At baseline, C3 and C4 levels were negatively associated with disease activity using the ns-SLEDAI score (p<0.04) but less consistently with the BILAG index score (p>0.06). Baseline natural log transformed EC4d and PC4d levels were both positively and significantly associated with the SLEDAI and BILAG scores (p<0.05). At the time of the follow-up visit (median 1.5 month, range 1-9 months from the baseline visit), there was a significant decrease in the SLEDAI (average decrease -2.4±0.4) and BILAG (average decrease -3.1±0.9) compared to baseline with linear mixed effects models indicating greater clinical improvement associated with the time to follow-up visit (Table). After adjusting for the time to follow-up, linear mixed effects model analysis revealed that the change in C3 or C4 levels correlated with the change in BILAG index scores (p<0.05) but less well with the ns-SLEDAI score (p>0.10). In contrast, the change in EC4d and BC4d correlated with the clinical change on both instruments (p<0.03). Finally, multivariate analysis of the change in the BILAG index score with PC4d, serum C3 and C4 as predictors (after adjusting for the time to follow-up) revealed that PC4d was associated with change in disease activity (slope estimate=1.80±0.76; p=0.02) while C3 and C4 were not (p>0.7).

Conclusion: These pilot findings suggest that cell bound complement measures could provide a sensitive marker for SLE disease improvement which might be useful for early optimization of treatment dosing.

Table Linear Mixed Effects Model Estimates