Lupus Science & Medicine
Table 5 Comparison of characteristics between cSLE patients with versus without high-level brain injury markers High-level marker group (n=13) Rest of cSLE group (n=43) P value Age at study visit, years 15.0 (14.0–16.0) 16.0 (13.0–17.0) 0.409 Female sex 13 (100) 35 (81) 0.093 Disease duration, months 2.0 (0.9–6.7) 9.2 (3.0–16.8) 0.006 Disease activity at visit (SLEDAI-2K) 6.0 (4.0–8.0) 2.5 (2.0–5.3) <0.001 * Adjusted mean SLEDAI-2K 9.8 (6.8–11.0) 2.5 (1.2–4.9) <0.001 * Damage (SDI >0) 3 (23) 2 (5) 0.041 IFN- α , pg/mL 0.86 (0.22–5.20) 0.20 (0.02–0.90) 0.056 IFN- γ , pg/mL 0.20 (0.08–0.30) 0.10 (0.06–0.20) 0.033 IL-6, pg/mL 3.16 (1.20–10.70) 1.00 (0.62–1.73) <0.001 * NPSLE diagnosis 0 (0) 1 (2) 0.579 Lupus nephritis 9 (69) 12 (26) 0.007 Anti-phospholipid antibody positive 2 (15) 10 (23) 0.544 Low C3/C4 12 (92) 27 (63) 0.043 DMARD use† (current) 9 (69) 21 (49) 0.196 Rituximab exposure (ever) 5 (39) 5 (12) 0.027 Current prednisone-equivalent dose, mg 10 (7.5–17.5) 0 (0–3.0) <0.001 * Cumulative prednisone-equivalent dose, g 7.0 (1.0–12.8) 1.6 (0–4.7) 0.107 Intravenous steroid use (ever) 5 (38) 9 (21) 0.201 Abnormal conventional brain MRI 1 (8) 9 (21) 0.275 Shown are exploratory comparisons of disease characteristics for cSLE patients with high-level brain injury markers (above the 90th percentile) versus those without high levels. Wilcoxon rank-sum tests were used for continuous variables (listed as median (IQR), unless otherwise specified) and χ 2 tests were used for categorical variables (listed as n (%)). P values <0.05 are shown in bold. *Indicates significance after Bonferroni correction (p<0.0025). †DMARD includes mycophenolate analogues or azathioprine or methotrexate. cSLE, childhood-onset systemic lupus erythematosus; IV, intravenous; NSPLE, neuropsychiatric SLE; SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.
We also note that we did not find associations between brain injury markers and other potential contributors to brain inflammation and injury such as complement- mediated factors and anti-phospholipid antibody status, 8 although we were under-powered to detect these. Simi- larly, there was no association between high-level markers and abnormalities on conventional brain MRI, but more sensitive neuroimaging may be needed to detect related changes, and this is an area for future study, as combining brain injury markers and neuroimaging has yielded diag- nostic advances in traumatic brain injury and multiple sclerosis. 35 36 Regarding the relationship between immunosuppres- sive treatment in brain injury markers, we found that the current GC dose was weakly correlated with sNFL, GFAP and Tau levels and was associated with having high-level markers in the cSLE group. In contrast, cumulative GC dose over the disease course was not correlated to indi- vidual brain injury markers. As disease activity is likely paralleled by GC use in this early disease cohort, we think these findings suggest cSLE disease activity to be the likely driver rather than GC effects. Nevertheless, it is possible that GCs can exert neurotoxic effects on the brain, 37 and
this warrants further study as there may be implications for further steroid-sparing efforts to support neuropro- tection. We did not find a difference in high-level brain injury marker status by disease-modifying antirheumatic drug use, although we were not powered for it. This is of interest for future study, given that a previous small study of youth and adults with NPSLE found that sNFL and GFAP serum levels declined with immunosuppressive therapy. 18 The limitations of our study include the cross-sectional design and relatively small sample size with only one NPSLE participant. We assessed overall CD across exec- utive function, attention and working memory, but other cognitive domains may also be affected. Although we looked at associations between brain injury markers and conventional clinical brain MRI abnormalities, we did not examine advanced neuroimaging such as diffusion tensor imaging, which provides more detail on microstructural brain tissue changes. We were also not able to look at the impact of different types of GCs (eg, intravenous vs oral) and specific immunosuppressive medications, and that is a future direction for study in a larger cohort. Addi- tionally, we did not look at additional cytokines (eg, IL-1
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Mwizerwa O, et al . Lupus Science & Medicine 2026; 13 :e001922. doi:10.1136/lupus-2025-001922
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