Childhood lupus
Elevated serum brain injury markers are associated with disease activity, pro- inflammatory cytokine levels and cognitive dysfunction in adolescents with childhood-onset SLE Oscar Mwizerwa , 1,2 Justine Ledochowski, 1 Ganesh Ramanathan, 1 Tala E Tal, 1,3 Sarah I Mossad, 1,4 Busi Zapparoli, 1,4 Lawrence Ng, 1 Asha Jeyanathan, 1 Adrienne Davis, 5,6 Linda T Hiraki, 6,7 Deborah M Levy , 6,7 Joan Wither , 8,9,10,11 Zahi Touma , 8,9,10,11 Ashley Danguecan, 4 Anne Yeh, 1,6,12 Andrea M Knight 1,6,7
To cite: Mwizerwa O, Ledochowski J, Ramanathan G, et al . Elevated serum
ABSTRACT Objective This study examined serum brain injury markers and their associations with disease features, cytokines associated with microglial activation in lupus and cognitive dysfunction (CD) in adolescents with childhood-onset SLE (cSLE). Methods We used cross-sectional data from cSLE patients (aged 12–17 years) and age-matched, sex-matched healthy controls. Serum levels of brain injury markers (serum neurofilament light, glial fibrillar acidic protein (GFAP), Tau), interferon (IFN)- α , IFN- γ and interleukin-6 (IL-6) were quantified using Simoa assays. cSLE features included disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000), damage (Systemic Lupus International Collaborating Clinics damage index) and glucocorticoid (GC) exposure. A neurocognitive battery assessed executive function, attention and working memory, and CD was determined using standardised scores. We compared brain injury marker levels between cSLE and controls, and those with and without CD using Wilcoxon rank-sum tests. We calculated correlations between injury markers, disease features and cytokines and examined differences in disease features between those with and without high-level brain injury markers (>90th percentile) (using Bonferroni correction). Results Participants included 56 cSLE patients (median disease duration=10.6 months (IQR 2.0–14.1), one with neuropsychiatric lupus) and 43 controls. Levels were higher in cSLE versus controls for GFAP (z=−3.97, p<0.001), Tau (z=−2.10, p=0.035), IFN- α (z=−4.80, p<0.001), IFN- γ (z=−2.42, p=0.015) and IL-6 (−3.09, p=0.002). Severe CD (≥2 SD from standardised mean) was present in 31% cSLE versus 9% controls (chi2=6.69, p=0.01), associated with higher Tau levels for cSLE (z=−3.94, p<0.001). High-level brain injury markers were observed in 13 (23%) cSLE patients associated with higher SLEDAI-2K, IL-6 levels and current GC dose. Conclusion Brain injury marker levels were high and associated with disease activity and CD in this cSLE adolescent cohort, suggesting a link between systemic inflammation and clinically under-detected neuronal/ glial injury. Larger, longitudinal studies should explore the
WHAT IS ALREADY KNOWN ON THIS TOPIC ⇒ Cognitive dysfunction (CD) affects approximate- ly one third of children with childhood-onset SLE (cSLE) during a critical period of neurodevelopment, yet attribution to neuropsychiatric SLE remains a clinical challenge due to the lack of diagnostic tools. ⇒ Brain injury markers such as serum neurofilament light (sNFL), glial fibrillar acidic protein (GFAP) and Tau have been used as diagnostic and monitoring biomarkers in neurologic and neuroinflammatory conditions; however, they have been understudied in cSLE. WHAT THIS STUDY ADDS ⇒ The results of this study show elevated serum lev- els of GFAP and Tau in children with cSLE compared with healthy controls, with 23% of the cSLE group showing severe CD despite the vast majority without a clinical neuropsychiatric lupus diagnosis. ⇒ Tau levels were associated with severe CD in chil- dren with cSLE, and those with high-level markers (across sNFL, GFAP and Tau) had higher disease ac- tivity, interleukin-6 levels and current glucocorticoid doses. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY ⇒ These findings indicate that brain injury is occurring in children with cSLE, even in the absence of neu- ropsychiatric lupus diagnosis, in association with elevated serum cytokines associated with microglial activation, providing mechanistic insight that may guide future development of clinical therapies. ⇒ These results suggest the potential utility of brain injury markers as diagnostic and monitoring bio- markers of CD due to cSLE and highlight the need for further study in larger, longitudinal cohorts.
brain injury markers are associated with disease activity, pro-inflammatory
cytokine levels and cognitive dysfunction in adolescents with childhood-onset SLE. Lupus Science & Medicine 2026; 13 :e001922. doi:10.1136/ lupus-2025-001922
Received 8 December 2025 Accepted 6 April 2026
For numbered affiliations see end of article. permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. Correspondence to Dr Andrea M Knight; andrea. knight@sickkids.ca © Author(s) (or their employer(s)) 2026. Re-use
potential clinical utility of brain injury markers for clinical assessment of brain involvement in cSLE.
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Mwizerwa O, et al . Lupus Science & Medicine 2026; 13 :e001922. doi:10.1136/lupus-2025-001922
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