Association of Elevated Serum S100A8/A9 Levels and Cognitive Impairment in Systemic Lupus Erythematosus Patients

Objectives Cognitive impairment (CI) is common in patients with Systemic Lupus Erythematosus (SLE). Despite its prevalence, the immune mechanisms are not well understood. We previously reported elevated serum levels of S100A8/A9 and MMP‐9 in SLE patients with CI. This study aims to validate those findings by examining the relationship between serum levels and CI in patients with SLE at baseline and after one year. Methods We assessed cognitive function in 112 SLE patients using the adapted ACR‐Neuropsychological Battery (ACR‐NB), defining CI as impairment in two or more domains. Serum S100A8/A9 and MMP‐9 levels were measured by ELISA. We compared serum levels between CI and non‐CI groups, evaluated cognitive domain performance at baseline and one year, and explored associations between serum changes and cognitive status changes. Results At baseline, 48 patients (42.8%) had CI. After one year, 55% remained stable, 31.2% improved, and 13% worsened. Serum S100A8/A9 levels were significantly higher in CI patients at baseline (p = 0.0007, r = 0.413) and one year (p = 0.0045, r = 0.359), correlating inversely with multiple CI domains. The worsened group showed a significant increase in S100A8/A9 levels, while the improved group exhibited a reduction. Conclusion In this large cohort of well‐characterized SLE patients, serum S100A8/A9 levels were elevated in those with CI and showed an inverse relationship with cognitive performance across multiple domains. Changes in S100A8/A9 levels corresponded with changes in cognitive status over one year. These findings warrant further investigation into the role of S100A8/A9 in CI within the context of SLE.