Association Between Systemic Inflammatory Response Biomarkers and Disease Activity in Systemic Lupus Erythematosus: A Multi-Center Retrospective Study

Objective: To evaluate the association of routine complete blood count (CBC)-derived inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI), with disease activity and exploratory neuropsychiatric risk stratification in patients with systemic lupus erythematosus (SLE). Methods: In this multi-center retrospective study, 579 SLE patients and 282 healthy controls (HCs) were recruited from five clinical centers between 2018 and 2025. NLR, MLR, PLR, and SIRI were calculated from routine CBC parameters. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), with high activity defined as SLEDAI-2K ≥ 10. The comparison between SLE patients and HCs was performed as an exploratory descriptive analysis to characterize systemic inflammatory profiles, whereas the primary analyses focused on associations with disease activity and NPSLE-related risk stratification. Results: SLE patients exhibited significantly higher levels of SIRI, NLR, PLR, and MLR compared to HCs (all p < 0.001). In this exploratory comparison, MLR showed the largest area under the curve for distinguishing SLE patients from HCs (AUC: 0.849, Cut-off: 0.263). In regression analyses, MLR, NLR, PLR, and SIRI were positively associated with SLEDAI-2K score. In multivariable linear regression analysis, MLR was associated with a higher SLEDAI-2K score (B = 4.600, 95% CI: 2.039–7.160, p < 0.001). In patients with available neuropsychiatric data, MLR, NLR, and SIRI were higher in patients with NPSLE than in those with non-NPSLE, whereas PLR showed no significant difference. SIRI showed modest exploratory discriminatory ability for NPSLE and may provide auxiliary information for NPSLE risk stratification (AUC: 0.710, p < 0.001, Cut-off: 1.438). Conclusions: Routine CBC-derived inflammatory biomarkers, particularly MLR, NLR, and SIRI, are associated with SLE disease activity and may serve as accessible, low-cost adjunctive tools for rapid clinical assessment. SIRI may provide additional auxiliary information for identifying patients at higher risk of neuropsychiatric involvement. However, these biomarkers should be interpreted as complementary screening or risk-stratification tools rather than substitutes for established disease activity indices or organ-specific evaluations. Further prospective studies are warranted to validate their clinical utility.