Anne B Tjensvoll1, Maria B Lauvsnes2, Henrik Zetterberg3,4,5,6, Jan T Kvaløy7,8, Ingeborg Kvivik7, Stian S Maroni9, Ole J Greve10, Mona K Beyer11,12, Shunsei Hirohata13, Chaim Putterman14,15,16, Guido Alves17,18, Erna Harboe2, Kaj Blennow3,4, Lasse G Gøransson2,19, Roald Omdal20,21. 1. Department of Neurology, Stavanger University Hospital, Stavanger, Norway. 2. Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway. 3. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 4. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At the University of Gothenburg, Mölndal, Sweden. 5. UK Dementia Research Institute At UCL, London, UK. 6. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 7. Research Department, Stavanger University Hospital, Stavanger, Norway. 8. Department of Mathematics and Physics, University of Stavanger, Stavanger, Norway. 9. Clinical Neuropsychology Unit, Division of Psychiatry, Stavanger University Hospital, Stavanger, Norway. 10. Department of Radiology, Stavanger University Hospital, Stavanger, Norway. 11. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 12. Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. 13. Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, 252-0374, Japan. 14. Division of Rheumatology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA. 15. Azrieli School of Medicine Bar-Ilan University, Zefat, Israel. 16. Galilee Medical Center Research Institute, Nahariya, Israel. 17. The Norwegian Centre for Movement Disorders and Department of Neurology, Stavanger University Hospital, Stavanger, Norway. 18. Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway. 19. Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway. 20. Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway. roald.omdal@lyse.net. 21. Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway. roald.omdal@lyse.net.
Abstract
BACKGROUND: To test the hypothesis that neurofilament light (NfL) in CSF is a biomarker of CNS involvement in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), we measured NfL in CSF from 52 patients with lupus and 54 with pSS and explored associations with clinical, structural, immunological and biochemical abnormalities. METHODS: In CSF, we measured NfL, anti-P antibodies, protein S100B and TWEAK by ELISA and anti-NR2 antibodies by electrochemiluminescence. Anti-phospholipid antibodies and routine immunological tests were performed in blood. IgG and albumin were measured in CSF and serum for assessment of the blood-brain barrier function (Q-albumin) and intrathecal IgG production (IgG index). Cerebral MRI and neuropsychological testing were performed. RESULTS: A multivariable regression model showed that increasing CSF anti-NR2 antibody levels were associated with increasing NfL levels in patients with SLE (B 1.27, 95% CI 0.88-1.65, p < 0.001). Age contributed significantly in the model (B 0.04, 95% CI 0.03-0.05, p < 0.001). Similar findings were observed in the pSS group. Adjusted for age and sex, no associations were found between NfL levels and any MRI data. In SLE patients, higher NfL concentrations were associated with impairments in psychomotor speed and motor function, and in pSS with motor dysfunction. These associations remained in multivariable regression models. CONCLUSIONS: Increased concentration of NfL in CSF is a marker of cerebral involvement in patients with SLE and pSS, is strongly associated with the presence of anti-NR2 antibodies, and correlates with cognitive impairment in several domains.
BACKGROUND: To test the hypothesis that neurofilament light (NfL) in CSF is a biomarker of CNS involvement in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), we measured NfL in CSF from 52 patients with lupus and 54 with pSS and explored associations with clinical, structural, immunological and biochemical abnormalities. METHODS: In CSF, we measured NfL, anti-P antibodies, protein S100B and TWEAK by ELISA and anti-NR2 antibodies by electrochemiluminescence. Anti-phospholipid antibodies and routine immunological tests were performed in blood. IgG and albumin were measured in CSF and serum for assessment of the blood-brain barrier function (Q-albumin) and intrathecal IgG production (IgG index). Cerebral MRI and neuropsychological testing were performed. RESULTS: A multivariable regression model showed that increasing CSF anti-NR2 antibody levels were associated with increasing NfL levels in patients with SLE (B 1.27, 95% CI 0.88-1.65, p < 0.001). Age contributed significantly in the model (B 0.04, 95% CI 0.03-0.05, p < 0.001). Similar findings were observed in the pSS group. Adjusted for age and sex, no associations were found between NfL levels and any MRI data. In SLEpatients, higher NfL concentrations were associated with impairments in psychomotor speed and motor function, and in pSS with motor dysfunction. These associations remained in multivariable regression models. CONCLUSIONS: Increased concentration of NfL in CSF is a marker of cerebral involvement in patients with SLE and pSS, is strongly associated with the presence of anti-NR2 antibodies, and correlates with cognitive impairment in several domains.
Authors: C Vitali; S Bombardieri; R Jonsson; H M Moutsopoulos; E L Alexander; S E Carsons; T E Daniels; P C Fox; R I Fox; S S Kassan; S R Pillemer; N Talal; M H Weisman Journal: Ann Rheum Dis Date: 2002-06 Impact factor: 19.103
Authors: P Scheltens; F Barkhof; D Leys; J P Pruvo; J J Nauta; P Vermersch; M Steinling; J Valk Journal: J Neurol Sci Date: 1993-01 Impact factor: 3.181
Authors: D Gladman; E Ginzler; C Goldsmith; P Fortin; M Liang; M Urowitz; P Bacon; S Bombardieri; J Hanly; E Hay; D Isenberg; J Jones; K Kalunian; P Maddison; O Nived; M Petri; M Richter; J Sanchez-Guerrero; M Snaith; G Sturfelt; D Symmons; A Zoma Journal: Arthritis Rheum Date: 1996-03
Authors: Maria Boge Lauvsnes; Henrik Zetterberg; Kaj Blennow; Jan Terje Kvaløy; Anne Bolette Tjensvoll; Stian Maroni; Mona K Beyer; Ole Jacob Greve; Ingeborg Kvivik; Guido Alves; Lasse Gunnar Gøransson; Erna Harboe; Shunsei Hirohata; Roald Omdal Journal: J Neurol Date: 2021-11-20 Impact factor: 4.849
Authors: John G Hanly; Alexandra Legge; Lyna Kamintsky; Alon Friedman; Javeria A Hashmi; Steven D Beyea; John Fisk; Antonina Omisade; Cynthia Calkin; Tim Bardouille; Chris Bowen; Kara Matheson; Marvin J Fritzler Journal: Lupus Sci Med Date: 2022-06