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
4 affiliations
- 1Schroeder Arthritis Institute, Krembil Research Institute, University Health Network , , ,
- 2University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital , , ,
- 3Library and Information Services, University Health Network, The Institute of Education Research, University Health Network , , ,
- 4Institute of Molecular Medicine, The Feinstein Institutes for Medical Research , , ,
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.
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BibTeX
@article{munozgrajales2026neuropsychiatric,
title = {{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}},
author = {Carolina Muñoz-Grajales and Sara Duaibes and Alan Cheng and Yasmin Nariman and Melanie Anderson and Dennisse Bonilla and Sindhu R. Johnson and Meggan Mackay and Joan Wither and Dafna D. Gladman and Zahi Touma},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1903757},
url = {https://europepmc.org/article/PMC/PMC13668822},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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
AU - Carolina Muñoz-Grajales
AU - Sara Duaibes
AU - Alan Cheng
AU - Yasmin Nariman
AU - Melanie Anderson
AU - Dennisse Bonilla
AU - Sindhu R. Johnson
AU - Meggan Mackay
AU - Joan Wither
AU - Dafna D. Gladman
AU - Zahi Touma
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1903757
UR - https://europepmc.org/article/PMC/PMC13668822
AB - 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.
SN - 1664-3224
ER -