Peripheral biomarkers of neuronal damage in neuropsychiatric systemic lupus erythematosus (NPSLE)

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with heterogeneous clinical presentations, including Neuropsychiatric SLE (NPSLE), which comprises a spectrum of central and peripheral nervous system manifestations attributable to immune-mediated neuronal and glial injury. Currently, diagnosing NPSLE is challenging due to the heterogeneous clinical manifestations and the lack of specific biomarkers. Breakthrough biomarkers are essential for improving diagnostic accuracy, prognostic assessment, and therapeutic monitoring in NPSLE. Serum biomarkers have been thoroughly examined, including inflammatory molecules such as cytokines, chemokines, and autoantibodies; however, these biomarkers are not brain-specific and have also been associated with other clinical domains of SLE. The present review focuses on neuronal and glial damage biomarkers in the context of NPSLE, highlighting their potential utility as diagnostic or prognostic biomarkers, while underscoring the need for further research in this area. Here, we discuss correlations between serum and cerebrospinal fluid (CSF) levels, supporting the use of serum as a minimally invasive surrogate for CNS assessment. Furthermore, findings on serum biomarkers of neurological damage were reviewed to explore their associations with clinical, demographic, and routine laboratory variables, which could provide insights into disease mechanisms. We identified potential biomarkers and highlighted important research gaps that may guide future investigations.