Childhood lupus
Figure 1 Comparison of brain injury markers between cSLE and controls. Legend: boxplots showing group comparison of brain injury marker levels between patients and controls. P value <0.05 was considered statistically significant (Wilcoxon rank- sum test). cSLE, childhood-onset SLE; GFAP, glial fibrillar acidic protein; sNFL, serum neurofilament light.
cSLE versus n=5 (12%) controls ( χ 2 =5.98, p=0.01). There were no significant differences in the presence of CD for the other cognitive domains. Relationships between brain injury markers and CD Table 3 shows comparisons of brain injury marker levels by CD status for cSLE and control participants. Tau levels were higher for cSLE patients with overall CD versus not (median 4.58 pg/mL, IQR 3.44–7.07 vs 2.64pg/mL, IQR 1.97–3.93, p<0.001) and with severe CD versus not (median 4.58 pg/mL, IQR 3.44–7.07 vs 2.74pg/mL, IQR 1.97–4.10, p<0.001), both statistically significant for a corrected p value <0.004. Relationship between brain injury markers and cSLE disease features Table 4 shows Spearman correlations between brain injury markers and disease features in the cSLE group. Higher Tau levels correlated with higher SLEDAI-2K at study visit (r=0.40, p=0.002) and AMS over the disease duration (r=0.49, p=0.002), although these did not reach statistical significance for a corrected p value <0.002. Disease features associated with high-level brain injury marker cSLE subgroup High-level markers were present in 13 (23%) patients with cSLE. Of these, six were elevated for one brain injury marker, six were elevated for two brain injury markers and one was elevated for all three brain injury markers. Table 5 shows comparisons of disease features between the high-level marker group and the rest of the cSLE group. The high- level marker group had a higher SLEDAI-2K level at study visit (median 6.0, IQR 4.0–8.0vs 2.5, IQR 2.0–5.3, p<0.001), AMS over the disease duration (median 9.8, IQR 6.8–11.0vs
patient had an NPSLE diagnosis. Conventional clinical brain MRI abnormalities were present in 10 (18%) of cSLE patients; these included T1 and T2 hyperintensities, T1 hypointensities and other abnormalities (eg, low-lying and/or rounded cerebellar tonsils, empty sella/flattened pituitary gland, cystic changes in pineal gland), none of which were attributed to cSLE. 23 (41%) were taking GCs, and the median cumulative GC dose was 2.9 grams (IQR 0.6–6.9). Additional participant characteristics are shown in table 1. Comparison of serum brain injury markers and cytokine levels between cSLE and control groups Figure 1 depicts group differences for cSLE versus controls showing higher levels of GFAP (median 114 pg/ mL, IQR 69–140vs 74pg/mL, IQR 55–92, p<0.0001) and Tau (median 3.6pg/mL, IQR 2.3–4.8vs controls 2.6pg/ mL, IQR 2–3, p=0.036). sNFL levels did not differ between groups (median 5.1pg/mL, IQR 4.2–7.8vs 4.8pg/mL, IQR 3.5–7.3, p=0.154). Table 2 shows higher levels of cytokines in the cSLE group versus controls, for IFN- α (median 0.28pg/mL, IQR 0.02–1.23vs 0.10pg/mL, IQR 0.06–0.23, p<0.0001), IFN- γ (median 0.07, IQR 0.05–0.10 vs 0.02 pg/mL, IQR 0.01–0.03, p=0.015) and IL-6 (median 1.20, IQR 0.72–2.65 vs 0.67, IQR 0.40–1.60, p=0.0018). CD in cSLE versus control participants Figure 2 depicts proportions of overall CD and domain- specific CD for cSLE and control participants. Overall CD was present in n=22 (38%) cSLE versus n=10 (23%) controls ( χ 2 =3.08, p=0.08), and severe CD was present in n=17 (31%) cSLE versus n=4 (9%) controls ( χ 2 =6.69, p=0.01). For domain-specific measures, CD for attention on the hit-reaction time task was present in n=18 (33%)
Table 2 Comparison of serum-IFN and IL-6 levels between cSLE and controls cSLE (n=56) Controls (n=43)
Median (IQR)
Range
Median (IQR)
Range
Z-statistic, P value
−4.80, <0.0001 −2.42, 0.015 −3.09, 0.0018
0.28 (0.02–1.23) 0.07 (0.05–0.10) 1.20 (0.72–2.65)
0–104.0 0–4.32
0.10 (0.06–0.23) 0.02 (0.01–0.03) 0.67 (0.40–1.60)
0.03–15.90 0.02–14.90 0.10–19.40
IFN- α (pg/mL) IFN- γ (pg/mL) IL-6 (pg/mL)
0.24–173.30
Shown are group comparisons of cytokine levels using the Wilcoxon rank-sum test; p values <0.05 are in bold and were considered statistically significant. cSLE, childhood-onset SLE; IFN- α , interferon alpha; IFN- γ , interferon gamma; IL-6, interleukin-6.
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Mwizerwa O, et al . Lupus Science & Medicine 2026; 13 :e001922. doi:10.1136/lupus-2025-001922
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