{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:14Z","timestamp":1790834474082,"version":"4.1.0"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to evaluate biomarkers that discriminate systemic lupus erythematosus patients with and without neuropsychiatric involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched MEDLINE, Embase, and CENTRAL (inception\u2014March 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 \u22655 independent studies; the remaining data were synthesized narratively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 93 studies were included. Few analyte\u2013biofluid 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\u2019\n                      <jats:italic>g<\/jats:italic>\n                      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\u20133.53), anti-NR2\/NMDAR (2.09, 1.07\u20134.06), and IgG anticardiolipin (2.36, 1.56\u20133.59) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1903757","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:10Z","timestamp":1790833270000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"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"],"prefix":"10.3389","volume":"17","author":[{"given":"Carolina","family":"Mu\u00f1oz-Grajales","sequence":"first","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network","place":["Toronto, ON, Canada"]},{"name":"University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital","place":["Toronto, ON, Canada"]},{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba","place":["Winnipeg, MB, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Duaibes","sequence":"additional","affiliation":[{"name":"University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Nariman","sequence":"additional","affiliation":[{"name":"University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Anderson","sequence":"additional","affiliation":[{"name":"Library and Information Services, University Health Network, The Institute of Education Research, University Health Network","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennisse","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network","place":["Toronto, ON, Canada"]},{"name":"University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindhu R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network","place":["Toronto, ON, Canada"]},{"name":"Institute of Health Policy, Management and Evaluation, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"Division of Rheumatology, Department of Medicine, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meggan","family":"Mackay","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, The Feinstein Institutes for Medical Research","place":["Manhasset, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Wither","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network","place":["Toronto, ON, Canada"]},{"name":"Department of Immunology and Division of Rheumatology, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"Department of Medicine, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna D.","family":"Gladman","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network","place":["Toronto, ON, Canada"]},{"name":"University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital","place":["Toronto, ON, Canada"]},{"name":"Division of Rheumatology, Department of Medicine, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahi","family":"Touma","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network","place":["Toronto, ON, Canada"]},{"name":"University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital","place":["Toronto, ON, Canada"]},{"name":"Division of Rheumatology, Department of Medicine, University of Toronto","place":["Toronto, ON, 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