Maria Boge Lauvsnes1, Henrik Zetterberg2,3,4,5, Kaj Blennow2,3, Jan Terje Kvaløy6,7, Anne Bolette Tjensvoll8, Stian Maroni9, Mona K Beyer10,11, Ole Jacob Greve12, Ingeborg Kvivik6, Guido Alves8,13,14, Lasse Gunnar Gøransson15,16, Erna Harboe15, Shunsei Hirohata17, Roald Omdal18,16. 1. Department of Rheumatology, Stavanger University Hospital, Pb. 8100 Forus, 4068, Stavanger, Norway. mariaboge@hotmail.com. 2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 3. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 4. UK Dementia Research Institute at UCL, London, UK. 5. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 6. Research Department, Stavanger University Hospital, Stavanger, Norway. 7. Department of Mathematics and Physics, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway. 8. Department of Neurology, Stavanger University Hospital, Stavanger, Norway. 9. Clinical Neuropsychology Unit, Division of Psychiatry, Stavanger University Hospital, Stavanger, Norway. 10. Instiute of Clinical Medicine, University of Oslo, Oslo, Norway. 11. Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. 12. Department of Radiology, Stavanger University Hospital, Stavanger, Norway. 13. The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. 14. Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway. 15. Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway. 16. Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway. 17. Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Sagamihara, Japan. 18. Department of Rheumatology, Stavanger University Hospital, Pb. 8100 Forus, 4068, Stavanger, Norway.
Abstract
BACKGROUND: Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. METHODS: Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. RESULTS: Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (β = 0.01, p < 0.001) and Q-albumin (β = 0.07, p = 0.008). We observed higher plasma NfL concentrations in patients with a history of seizures (β = 0.57, p = 0.014), impaired motor function (β = 0.36, p = 0.008), increasing disease activity (β = 0.04, p = 0.008), and organ damage (β = 0.10, p = 0.002). Voxel-based morphometry suggested an association between increasing plasma NfL concentrations and the loss of cerebral white matter in the corpus callosum and hippocampal gray matter. CONCLUSION: Increased plasma NfL concentrations were associated with some abnormal neurological, cognitive, and neuroimaging findings. However, plasma NfL was also influenced by other factors, such as damage accrual, creatinine, and Q-albumin, thereby obscuring the interpretation of how plasma NfL reflects CNS involvement. Taken together, NfL in CSF seems a better marker of neuronal injury than plasma NfL in patients with SLE.
BACKGROUND: Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. METHODS: Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. RESULTS: Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (β = 0.01, p < 0.001) and Q-albumin (β = 0.07, p = 0.008). We observed higher plasma NfL concentrations in patients with a history of seizures (β = 0.57, p = 0.014), impaired motor function (β = 0.36, p = 0.008), increasing disease activity (β = 0.04, p = 0.008), and organ damage (β = 0.10, p = 0.002). Voxel-based morphometry suggested an association between increasing plasma NfL concentrations and the loss of cerebral white matter in the corpus callosum and hippocampal gray matter. CONCLUSION: Increased plasma NfL concentrations were associated with some abnormal neurological, cognitive, and neuroimaging findings. However, plasma NfL was also influenced by other factors, such as damage accrual, creatinine, and Q-albumin, thereby obscuring the interpretation of how plasma NfL reflects CNS involvement. Taken together, NfL in CSF seems a better marker of neuronal injury than plasma NfL in patients with SLE.
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