NPSLE is a diagnostically challenging manifestation of SLE, with prevalence widely ranging from 12% to 95%, highlighting the importance of a reliable biomarker for its diagnosis. NfL, measurable in serum and CSF, has shown promising but inconsistent results across individual studies, warranting a systematic review and meta-analysis

We systematically searched PubMed, Embase, Scopus, and Web of Science up to May 2026 for observational studies on neurofilament light chain (NfL) in SLE and neuropsychiatric SLE (NPSLE). Data were independently extracted, and study quality was assessed using the Newcastle–Ottawa Scale (NOS). Data were analyzed using RevMan 5.4, pooling standardized mean differences (SMDs) with 95% confidence intervals (CIs) using fixed-effects models for serum analyses and random-effects models where appropriate; heterogeneity was assessed using I² with sensitivity analyses

Five studies published between 2021 and 2025 were included in this systematic review, four of which were eligible for statistical pooling. For serum NfL, a meta-analysis of three studies (163 NPSLE vs. 117 non-NPSLE patients) demonstrated significantly higher levels in NPSLE patients (SMD = 0.34, 95% CI: 0.09–0.59, p = 0.007, I² = 14%). For CSF NfL, a meta-analysis of two studies (40 NPSLE vs. 40 non-NPSLE patients) showed no statistically significant difference (SMD = 2.62, 95% CI: -1.22–6.45, p = 0.18), with high heterogeneity between studies (I² = 97%)

Serum NfL levels were significantly elevated in NPSLE patients compared to non-NPSLE patients, supporting its potential as a promising non-invasive biomarker for neuropsychiatric involvement in SLE. CSF NfL findings were inconclusive, largely driven by high heterogeneity. These findings highlight the need for larger standardized prospective studies to further establish the clinical utility of NfL as a diagnostic and monitoring biomarker in NPSLE