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Low complement items play different roles on the classification performance of SLICC-2012, EULAR/ACR-2019, and SLERPI
Shanshan Chen1, Lin Zhang2, Mengxue Yan1
1Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Insights
Low complement levels significantly enhance sensitivity in systemic lupus erythematosus (SLE) classification criteria like SLICC-2012. Excluding this item impacts sensitivity and specificity, but combined low C3 and C4 levels remain clinically relevant.
Area of Science:
- Rheumatology
- Immunology
- Clinical Diagnostics
Background:
- Systemic lupus erythematosus (SLE) classification criteria are crucial for diagnosis and management.
- Low complement levels (hypocomplementemia) are common in SLE but their impact on classification performance is debated.
- Existing criteria include complement levels, but their diagnostic utility requires further investigation.
Purpose of the Study:
- To evaluate the association between low complement levels and the performance of SLE classification criteria.
- To compare the sensitivity and specificity of SLICC-2012, EULAR/ACR-2019, and SLERPI before and after excluding low complement items.
- To assess the clinical significance of low C3 and C4 levels in SLE patients.
Main Methods:
- Retrospective analysis of 352 SLE patients and 385 individuals with positive antinuclear antibodies.
- Comparison of SLICC-2012, EULAR/ACR-2019, and SLERPI performance with and without the low complement item.
- Analysis of clinical characteristics associated with low C3 and C4 levels.
Main Results:
- Excluding low complement decreased sensitivity but increased specificity for SLICC-2012 and EULAR/ACR-2019.
- SLERPI showed stable classification performance after excluding low complement.
- Patients with both low C3 and C4 levels had distinct clinical features and higher classification scores.
Conclusions:
- Low complement levels significantly improve the sensitivity and early classification of SLE, particularly for SLICC-2012.
- The combined assessment of low C3 and C4 levels holds clinical relevance in SLE classification.
- SLERPI demonstrates robust performance irrespective of complement levels.
Objectives:
This study aimed to explore the association of low complement items with the performance of the systemic lupus erythematosus (SLE) classification criteria.
Methods:
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.
Results:
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.
Conclusion:
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.
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