Cell-Bound Complement Activation Products May Help Pediatric-Onset SLE Diagnosis

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CB-CAPs have higher sensitivity and specificity and may help with diagnosis of pediatric-onset SLE.
CB-CAPs have higher sensitivity and specificity and may help with diagnosis of pediatric-onset SLE.

In patients with pediatric-onset systemic lupus erythematosus (SLE), cell-bound complement activation products (CB-CAPs), or stable deposits of complement activation products on erythrocytes (EC4d) and B lymphocytes (BC4d), have higher sensitivity and specificity than low complement, and may assist in the diagnosis and monitoring of the disease, according to prospective cohort study data published in Lupus.1

Eligible patients met ≥4 of 11 revised criteria from the 1997 American College of Rheumatology for a diagnosis of pediatric-onset SLE (SLE onset ≤19 years).2 Patients who met the criteria for a juvenile idiopathic arthritis (JIA) diagnosis served as disease controls.3 A total of 28 patients with pediatric-onset SLE and 22 patients with JIA were enrolled in the study. SLE disease activity was evaluated using the clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), which excluded serologies. Abnormal CB-CAPs were defined as EC4d or BC4d above the 99th percentile in healthy adults.

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Performance characteristics of CB-CAPs were evaluated using area under the curve (AUC) for receiver operating characteristics. Linear mixed models were used to assess the correlation between CB-CAPs and clinical SLEDAI over 6 months. Autoantibodies were calculated using sold-phase immunoassays, C3 and C4 were measured using immunoturbidimetry, and CB-CAPs were measured using quantitative flow cytometry.

Study results showed that BC4d generated significantly higher AUC (0.91 ± 0.04) than C3 (0.63±0.08) and C4 (0.67±0.08; P <.05). Moreover, abnormal CB-CAPs were 86% specific and 76% sensitive for the diagnosis of pediatric-onset SLE (Youden's index, 0.64 ± 0.11). Compared with BC4d, EC4d levels correlated significantly with clinical SLEDAI (P <.01).

The investigators concluded that in patients with pediatric-onset SLE, EC4d could provide a useful biomarker for the monitoring of disease activity. The high specificity and sensitivity of BC4d for the diagnosis of pediatric-onset SLE compared with patients with JIA, along with the correlation demonstrated between EC4d and disease activity measures, further supports the importance of CB-CAPs in the pathogenesis of pediatric-onset SLE. Additional research is warranted in order to determine the role played by CB-CAPs in pediatric patients with SLE.

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References

  1. Hui-Yuen JS, Gartshteyn Y, Ma M, et al. Cell-bound complement activation products (CB-CAPs) have high sensitivity and specificity in pediatric-onset systemic lupus erythematosus and correlate with disease activity [published online October 30, 2018]. Lupus. doi:10.1177/0961203318809181
  2. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
  3. Cassidy JT, Levinson JF, Bass JC, et al. A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum. 1986;29(2):274-281.
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