Childhood lupus
beta and TNF-alpha) and individual complement cascade proteins, which have been implicated in microglial acti- vation and brain injury. Larger, longitudinal studies will enable further investigation of these important gaps. Nevertheless, the strengths of our study lie in its investigation of multiple brain injury markers in a well- characterised cSLE cohort and inclusion of age-matched and sex-matched controls. CONCLUSION In our investigation of brain injury markers sNFL, GFAP and Tau in adolescents with cSLE, we found elevated levels of GFAP and Tau and almost 25% had very high levels across all three markers. Brain injury in this early disease cohort, at a critical neurodevelopmental period and largely without clinical NPSLE diagnosis, was asso- ciated with active disease, systemic pro-inflammatory cytokines and CD, suggesting inflammation-driven brain injury impacting function. Our study highlights the value of examining sNFL, GFAP, Tau and other neurological biomarkers collectively to broaden our understanding of mechanisms underlying brain involvement in cSLE and guide advances in the diagnosis and treatment of NPSLE. Importantly, our findings suggest that CD in cSLE may be under-detected and under-treated by the current standard of care, indicating a potential role for neuro- protective strategies and targeted cognitive interventions. Further studies in larger, longitudinal cohorts are needed to confirm our findings and determine trajectories of brain injury as well as temporal relationships to cSLE disease activity, damage and treatment. Author affiliations 1 Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada 2 Pediatrics & Rheumatology, Dr. Georges‑L.‑Dumont University Hospital Centre, Moncton, New Brunswick, Canada 3 Division of Rheumatology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada 4 Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada 5 Department of Pediatric Emergency Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada 6 Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada 7 Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada 8 University Health Network, Toronto, Ontario, Canada 9 Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada 10 Medicine, University of Toronto, Toronto, Ontario, Canada 11 Division of Rheumatology, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada 12 Department of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada Acknowledgements We thank all the families, patients, parents and caregivers who participated in the study and allowed us to use their samples and data for this work. Parts of this work have previously been presented as meeting abstracts at the American College of Rheumatology Convergence 2024, International Neuropsychological Society 2025, Canadian Rheumatology Association Meeting 2024 & 2025, Lupus International Congress 2025 and Paediatric Rheumatology European Society 2025. Contributors OM: conceptualisation, methodology, formal analysis, visualisation, interpretation, writing—original draft and review and editing; JL: conceptualisation, methodology, validation, writing—review and editing; GR: data visualisation, formal analysis, interpretation, writing—original draft and review and editing; TET, SM,
AdD, LTH, DML, JW, ZT and AY: writing—review and editing; BZ: methodology, writing—review and editing; LN: data curation, project management, writing— review and editing; AJ: data curation, project management, writing—reviewing and editing; AsD: methodology, writing—review and editing; AMK: conceptualisation, methodology, investigation, funding acquisition, resources, validation, writing— review and editing, supervision. AK: guarantor. Funding This work was supported by the Lupus Research Alliance (Novel Research Grant No. 481569 and Empowering Lupus Research Career Development Award No. 935840 to AMK), US Department of Defense (Lupus Research Program Impact Award No. W81XWH-20-1-0560 to AMK), Lupus Foundation of America (Gina M. Finzi Memorial Student Summer Fellowship Award to GR), Canada Institutes of Health Research (Canada Research Chair Tier 2 Award No. PCS-190986 to AMK) and SickKids Garry Hurvitz Centre for Brain & Mental Health (Capitalize for Kids Pediatric Mental Health Fellowship Award to OM). Competing interests None declared. Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research. Patient consent for publication Not applicable. Ethics approval This study involves human participants and was approved by The Hospital for Sick Children Research Ethics Board (REB# 1000071306, REB# 1000063027, REB# 1000080072). Participants gave informed consent to participate in the study before taking part. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available upon reasonable request. The datasets generated and analysed during the current study are available from the corresponding author on reasonable request. Due to patient confidentiality, the datasets will not be publicly shared. Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.
ORCID iDs Oscar Mwizerwa https://orcid.org/0000-0001-8322-7494 Deborah M Levy https://orcid.org/0000-0003-1023-9499 Joan Wither https://orcid.org/0000-0001-5961-9228 Zahi Touma https://orcid.org/0000-0001-5177-2076 Andrea M Knight https://orcid.org/0000-0003-4278-9049
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Mwizerwa O, et al . Lupus Science & Medicine 2026; 13 :e001922. doi:10.1136/lupus-2025-001922
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