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Cell-bound complement activation products associate with lupus severity in SLE
Cristina Arriens1,2, Roberta Vezza Alexander3, Sonali Narain4
1Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Insights
Cell-bound complement activation products (CB-CAPs) indicate lupus severity, unlike low C3/C4 levels. Abnormal CB-CAPs correlate with higher Lupus Severity Index (LSI) scores, suggesting their utility in assessing disease activity.
Area of Science:
- Immunology
- Rheumatology
- Systemic Lupus Erythematosus (SLE) research
Background:
- Complement system activation plays a role in SLE pathogenesis.
- Cell-bound complement activation products (CB-CAPs) and complement protein levels (C3, C4) are potential biomarkers for SLE activity.
Purpose of the Study:
- To investigate the association between lupus severity, measured by the Lupus Severity Index (LSI), and the presence of CB-CAPs or low C3/C4 levels.
- To determine the predictive value of CB-CAPs and low complement proteins for SLE disease severity.
Main Methods:
- A cohort of 495 SLE patients meeting ACR criteria was analyzed.
- CB-CAPs (erythrocyte-bound C4d, B-lymphocyte-bound C4d) and serum C3/C4 levels were quantified.
- Lupus severity was assessed using the LSI, with statistical analysis including multivariable linear regression.
Main Results:
- Abnormal CB-CAPs were more frequent (62%) than low C3/C4 (38%).
- Higher LSI scores were observed in patients with abnormal CB-CAPs and those with both abnormal CB-CAPs and low C3/C4.
- Multivariable analysis confirmed that abnormal CB-CAPs, but not low C3/C4, were independently associated with increased LSI scores, even after adjusting for age, race, and disease duration.
Conclusions:
- Abnormalities in complement activation, specifically CB-CAPs, are significantly associated with increased SLE severity (LSI).
- CB-CAPs may serve as a more sensitive indicator of disease activity in SLE compared to low C3/C4 levels.
Objectives:
To evaluate the association between lupus severity and cell-bound complement activation products (CB-CAPs) or low complement proteins C3 and C4.
Methods:
All subjects (n=495) fulfilled the American College of Rheumatology (ACR) classification criteria for SLE. Abnormal CB-CAPs (erythrocyte-bound C4d or B-lymphocyte-bound C4d levels >99th percentile of healthy) and complement proteins C3 and C4 were determined using flow cytometry and turbidimetry, respectively. Lupus severity was estimated using the Lupus Severity Index (LSI). Statistical analysis consisted of multivariable linear regression and groups comparisons.
Results:
Abnormal CB-CAPs were more prevalent than low complement values irrespective of LSI levels (62% vs 38%, respectively, p<0.0001). LSI was low (median 5.44, IQR: 4.77-6.93) in patients with no complement abnormality, intermediate in patients with abnormal CB-CAPs (median 6.09, IQR: 5.31-8.20) and high in the group presenting with both abnormal CB-CAPs and low C3 and/or C4 (median 7.85, IQR: 5.51-8.37). Odds of immunosuppressant use was higher in subjects with LSI ≥5.95 compared with subjects with LSI <5.95 (1.60 vs 0.53, p<0.0001 for both). Multivariable regression analysis revealed that higher LSI scores associated with abnormal CB-CAPs-but not low C3/C4-after adjusting for younger age, race and longer disease duration (p=0.0001), which were also independent predictors of disease severity (global R2=0.145).
Conclusion:
Abnormalities in complement activation as measured by CB-CAPs are associated with increased LSI.
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