{
  "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 potential clinical utility of brain injury markers for clinical assessment of brain involvement in cSLE.",
  "authors": [
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada",
        "Pediatrics & Rheumatology, Dr. Georges‑L.‑Dumont University Hospital Centre, Moncton, New Brunswick, Canada"
      ],
      "name": "Oscar Mwizerwa"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Justine Ledochowski"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Ganesh Ramanathan"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada",
        "Division of Rheumatology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada"
      ],
      "name": "Tala E Tal"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada",
        "Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Sarah I Mossad"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada",
        "Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Busi Zapparoli"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Lawrence Ng"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Asha Jeyanathan"
    },
    {
      "affiliations": [
        "Department of Pediatric Emergency Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada",
        "Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Adrienne Davis"
    },
    {
      "affiliations": [
        "Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada",
        "Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Linda T Hiraki"
    },
    {
      "affiliations": [
        "Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada",
        "Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Deborah M Levy"
    },
    {
      "affiliations": [
        "University Health Network, Toronto, Ontario, Canada",
        "Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada",
        "Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Division of Rheumatology, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada"
      ],
      "name": "Joan Wither"
    },
    {
      "affiliations": [
        "University Health Network, Toronto, Ontario, Canada",
        "Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada",
        "Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Division of Rheumatology, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada"
      ],
      "name": "Zahi Touma"
    },
    {
      "affiliations": [
        "Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Ashley Danguecan"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada",
        "Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada",
        "Department of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Anne Yeh"
    },
    {
      "affiliations": [
        "Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada",
        "Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada",
        "Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Andrea M Knight"
    }
  ],
  "title": "Elevated serum brain injury markers are associated with disease activity, pro-inflammatory cytokine levels and cognitive dysfunction in adolescents with childhood-onset SLE",
  "uid": "c90ec45c-94bf-5470-8049-de4ea37ea87b"
}