Association of elevated serum S100A8/A9 levels and cognitive impairment in patients with systemic lupus erythematosus

OBJECTIVE: 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 matrix metalloproteinase 9 (MMP-9) in patients with SLE and 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 patients with SLE using the adapted American College of Rheumatology-Neuropsychological Battery, defining CI as impairment in two or more domains. Serum S100A8/A9 and MMP-9 levels were measured by enzyme-linked immunosorbent assay. 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, the cognitive funtion remained stable in 55%, improved in 31.2%, and worsened in 13% of patients. 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, whereas the improved group exhibited a reduction. CONCLUSION: In this large cohort of patients with well-characterized SLE, 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