Work

The neuropsychiatric systemic lupus erythematosus biomarker landscape: what blood and cerebrospinal fluid analytes have been studied and how they performed? A systematic review and meta-analysis

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Objective This study aims to evaluate biomarkers that discriminate systemic lupus erythematosus patients with and without neuropsychiatric involvement. Methods We searched MEDLINE, Embase, and CENTRAL (inception—March 2024) for studies of blood or cerebrospinal fluid (CSF) analytes in neuropsychiatric systemic lupus erythematosus (NPSLE). Random-effects meta-analyses were conducted for analyte-biofluid pairs with ≥5 independent studies; the remaining data were synthesized narratively. Results A total of 93 studies were included. Few analyte–biofluid combinations met the criteria for meta-analysis, and most promising biomarkers (intrathecal inflammation, neuronal injury, and reduced neuroprotection) were assessed in only small, heterogeneous studies. The meta-analyses showed higher CSF IL-6 and MCP-1 in NPSLE than non-NPSLE SLE (Hedges’ g 0.81 and 0.66, respectively), a smaller heterogeneous effect for IL-8, and two- to threefold higher odds of NPSLE in patients positive for serum anti-ribosomal P (OR 2.68, 95% CI 2.03–3.53), anti-NR2/NMDAR (2.09, 1.07–4.06), and IgG anticardiolipin (2.36, 1.56–3.59) antibodies. Compared with non-SLE controls, NPSLE generally showed higher CSF soluble mediators than healthy or non-inflammatory neurological comparators, but the levels in CNS infections were often similar or higher. Conclusion CSF markers of intrathecal inflammation, neuronal injury, and reduced neuroprotection distinguish NPSLE from non-NPSLE SLE but are neither specific for NPSLE nor easily obtainable in routine practice. Classical serum autoantibodies (anti-ribosomal P, anti-NR2, and antiphospholipid antibodies) show modest, phenotype-dependent diagnostic performance. Evidence remains fragmented, with heterogeneous assays, cutoffs, and case definitions, underscoring the need for harmonized multicenter studies to identify robust diagnostic, evaluative, and prognostic biomarkers for overall and manifestation-specific NPSLE.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1903757