Systemic Immune-Inflammation Index (SII) correlates with disease activity but not with interferon-associated chemokines in SLE

Objective The Systemic Immune-Inflammation Index (SII) is an accessible haematological marker reflecting systemic inflammatory burden. In SLE, type I interferon-associated chemokines have been proposed as biomarkers of disease activity. This study evaluated the discriminatory performance of the SII between patients with SLE and healthy individuals and its correlation with disease activity and circulating interferon-associated chemokines.Methods In this cross-sectional study, we analysed data from 95 women with SLE and 1443 healthy female controls from two established cohorts. The SII was calculated as (neutrophil count × platelet count) / lymphocyte count. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K). Serum levels of CCL11/eotaxin-1, CCL2/MCP-1, CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CXCL10/IP-10, CXCL12/SDF-1α, CXCL1/GRO-α and CXCL8/IL-8 were quantified using a multiplex assay.Results Median SII values were significantly higher in patients with SLE than in healthy controls (588.8 (IQR 390.8–964.8) vs 521.4 (IQR 381.6–690.5); p=0.022), though its discriminatory performance was limited (area under the curve (AUC)=0.57; 95% CI 0.49 to 0.64; p=0.022). Within the SLE cohort, the SII correlated positively with SLEDAI-2K scores (Spearman’s ρ=0.303; 95% CI 0.102 to 0.480; p=0.003), but showed no significant correlations with any circulating chemokines. Conversely, SLEDAI-2K scores initially demonstrated nominal positive correlations with serum CCL5/RANTES (ρ=0.257; 95% CI 0.008 to 0.475; unadjusted p=0.037) and CXCL8 (ρ=0.228; 95% CI 0.012 to 0.422; unadjusted p=0.032); however, no chemokine maintained statistical significance after false discovery rate multiple-testing correction.Conclusion Although the SII correlates with overall SLE disease activity, it does not reflect circulating concentrations of interferon-associated chemokines.