Background/Purpose: Elevated cell-bound complement activation products (CBCAPs) and decreased erythrocyte complement receptor 1 (ECR1) expression may correlate with disease activity in systemic lupus erythematosus (SLE). We evaluated the relationship between CBCAPs, ECR1 and SLE disease activity as part the multicenter study of complement activation products in the assessment of lupus (CAPITAL).

Methods: The CAPITAL study was cross-sectional and enrolled SLE patients who met the ACR classification criteria. ECR1 as well as complement C4d levels on erythrocytes (EC4d), platelets (PC4d), and B cells (BC4d) were determined using flow cytometry. Disease activity was measured at the time of the study visit using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI). Disease activity was dichotomously stratified by SELENA-SLEDAI scores <6 (low disease activity) or ≥6 (high disease activity). Statistical analyses utilized Wilcoxon rank-sum tests, area under receiver operating characteristic (ROC) curves, Fisher Exact tests and multivariate logistic regression.

Results: Among 209 SLE evaluable patients (90% females, mean age 41years), a total of 41 (19.6%) had high disease activity at the time of sample acquisition. As presented in Table I, high disease activity was associated with elevated levels of EC4d, BC4d, PC4d and reduced levels of ECR1 (p<0.004).  ROC analyses indicated that EC4d above 14.8 units (ROC AUC=0.646) was associated with a 3.4-fold (95% CI: 1.6-7.4) higher likelihood of high disease activity. Similarly, BC4d above 71.5 units (ROC AUC=0.643) and PC4d above 6.3 units (ROC AUC=0.718) were associated with a 4.3-fold (95% CI:1.9-10.8) and 5.3-fold (95% CI:2.3-13.5) greater likelihood of high disease activity, respectively. Conversely, ECR1 levels below 10 net MFI (AUC=0.694) were associated with a 4.2-fold (95% CI:1.9-9.3) higher likelihood of high disease activity. By multivariate logistic regression analysis only elevated PC4d and low ECR1 were associated with high disease activity. Among patients presenting with both elevated PC4d (>6.3 net MFI) and reduced ECR1 (<10.2 net MFI), 45% had high disease activity compared to 5% of those having PC4d and ECR1 below 6.3 and above 10.2 net MFI respectively (p<0.01). 

Table: CB-CAPS and ECR1 levels in SLE patients with low or high disease activity (MFI: mean fluorescence intensity)

Conclusion: These hypothesis generating data suggest that elevated EC4d, BC4d, PC4d and reduced ECR1 levels are associated with high disease activity. Prospective longitudinal studies will be essential to establish the predictive value of CBCAPs and ECR1 measurements for determining SLE disease flares.