Cell-bound complement activation products (CB-CAPs) have high sensitivity and specificity in pediatric-onset systemic lupus erythematosus and correlate with disease activity

Lupus. 2018 Dec;27(14):2262-2268. doi: 10.1177/0961203318809181. Epub 2018 Oct 30.


Objective: Elevated levels of cell-bound complement activation products (CB-CAPs) (C4d deposition on B lymphocytes (BC4d) and/or erythrocytes (EC4d)) are sensitive and specific in diagnosis and monitoring of adult systemic lupus erythematosus (SLE). Our objective was to evaluate the role of CB-CAPs for diagnosis and monitoring of pediatric-onset SLE (pSLE).

Methods: A prospective cohort study of 28 pSLE and 22 juvenile arthritis patients was conducted. SLE disease activity was determined using a clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) that excluded serologies. Autoantibodies were measured using solid-phase immunoassays, C3 and C4 using immunoturbidimetry, and CB-CAPs using quantitative flow cytometry. Abnormal CB-CAPs were defined as EC4d or BC4d above the 99th percentile for healthy adults (>14 and > 60 net mean fluorescence intensity (MFI), respectively). Performance characteristics of CB-CAPs were assessed using area under the curve (AUC) for receiver operating characteristics. Linear mixed effect models evaluated the correlation between CB-CAPs and clinical SLEDAI over 6 months.

Results: BC4d yielded higher AUC (0.91 ± 0.04) than C3 (0.63 ± 0.08) and C4 (0.67 ± 0.08) ( p < 0.05). Abnormal CB-CAPs were 78% sensitive and 86% specific for diagnosis of pSLE (Youden's index = 0.64 ± 0.11). In contrast to BC4d, EC4d levels correlated with clinical SLEDAI ( p < 0.01).

Conclusion: CB-CAPs (EC4d and BC4d) have higher sensitivity and specificity than low complement in pSLE, and may help with diagnosis of pSLE. EC4d could provide a useful biomarker for disease activity monitoring.

Keywords: Cell-bound complement activation products; lupus; pediatric.

MeSH terms

  • Adolescent
  • Age of Onset
  • Autoantibodies / blood*
  • Biomarkers / metabolism*
  • Complement Activation
  • Complement System Proteins / metabolism*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoassay
  • Lupus Erythematosus, Systemic / diagnosis*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Prospective Studies
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Young Adult


  • Autoantibodies
  • Biomarkers
  • Complement System Proteins