Research Article: Low complement items play different roles on the classification performance of SLICC-2012, EULAR/ACR-2019, and SLERPI
Abstract:
This study aimed to explore the association of low complement items with the performance of the systemic lupus erythematosus (SLE) classification criteria.
This study included 352 patients with SLE and 385 individuals with positive antinuclear antibodies with other diseases. The performance of the Systemic Lupus International Collaborating Clinics (SLICC)-2012, European League Against Rheumatism and American College of Rheumatology (EULAR/ACR)-2019, and SLE Risk Probability Index (SLERPI) were compared before and after excluding the low complement item.
The exclusion of the low complement item decreased the sensitivity and increased the specificity of SLICC-2012 and EULAR/ACR-2019, whereas SLERPI demonstrated stable classification performance in classifying patients with and without SLE. SLICC-2012 exhibited the highest sensitivity in identifying patients with SLE with hypocomplementemia (99.0%; 95% confidence interval [CI]: 97.2–99.8%), followed by SLERPI (98.4%; 95% CI: 96.3–99.5%) and EULAR/ACR-2019 (97.7%; 95% CI: 95.4–99.1%). After excluding the low complement item, the sensitivities decreased to 93.0% (89.5–95.5%) for SLICC-2012, 97.5% (86.8–99.9%) for SLERPI, and 93.3% (90.0–95.8%) for EULAR/ACR-2019. SLICC-2012, EULAR/ACR-2019, and SLERPI identified 16, 17, and 21 patients with SLE with hypocomplementemia before clinical diagnosis, decreasing to 10, 16, and 20 cases after excluding the low complement item. Further, patients with SLE with both low C3 and C4 levels demonstrated shorter disease duration, higher acute cutaneous lupus prevalence, nonscarring alopecia, and increased positivity rates for anti-DNA antibodies, antiphospholipid antibodies, and direct Coombs’ tests compared with those with low C3 or C4 levels. The SLE group with low C3 and C4 levels demonstrated significantly higher total scores than the SLE group with low C3 or C4 levels in all three classification criteria, and this significance persisted even after excluding the low complement item.
The low complement item strongly improved the sensitivity and early classification capacity of SLICC-2012 while minimally influencing SLERPI. Furthermore, higher weights assigned to combined low C3 and C4 levels in EULAR/ACR-2019 appear clinically justified.
Introduction:
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is characterized by the presence of autoantibodies against nuclear antigens, immune complex deposits, and chronic inflammation of typical target organs ( 1 ). The complement system plays multiple roles in the pathogenesis of SLE, such as clearing immune complexes, promoting inflammatory responses, eliminating apoptotic cells, and regulating B-cell activation for autoantibody production ( 2 ). Low complement levels are a hallmark of SLE and…
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