Neurofilament light in plasma is a potential biomarker of central nervous system involvement in systemic lupus erythematosus.
Biomarker
Central nervous system
Cerebral imaging
Neurofilament light
Systemic lupus erythematosus
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
09
09
2021
accepted:
05
11
2021
revised:
04
11
2021
pubmed:
21
11
2021
medline:
24
5
2022
entrez:
20
11
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 34800169
doi: 10.1007/s00415-021-10893-z
pii: 10.1007/s00415-021-10893-z
doi:
Substances chimiques
Albumins
0
Biomarkers
0
Neurofilament Proteins
0
neurofilament protein L
0
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3064-3074Subventions
Organisme : Helse Vest
ID : F-12525
Organisme : Helse Vest
ID : 912129
Organisme : Helse Vest
ID : 911807
Organisme : Vetenskapsrådet
ID : 2018-02532
Organisme : Vetenskapsrådet
ID : 2017-00915
Organisme : H2020 European Research Council
ID : 681712
Organisme : Swedish State Support for Clinical Research
ID : ALFGBG-720931
Organisme : Alzheimer's Drug Discovery Foundation
ID : 201809-2016862
Organisme : The Swedish Alzheimer's Foundation
ID : AF-742881
Organisme : Hjärnfonden
ID : FO2017-0243
Organisme : the European Union Joint Program for Neurodegenerative Disorders
ID : JPND2019-466-236
Organisme : Norges Forskningsråd
ID : 287842
Organisme : Japan Agency for Medical Research and Development
ID : 15eK0410022h0001
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
Références
Hanly JG, Kozora E, Beyea SD, Birnbaum J (2019) Review: nervous system disease in systemic lupus erythematosus: current status and future directions. Arthritis Rheumatol (Hoboken, NJ) 71(1):33–42. https://doi.org/10.1002/art.40591
doi: 10.1002/art.40591
Faust TW, Chang EH, Kowal C, Berlin R, Gazaryan IG, Bertini E, Zhang J, Sanchez-Guerrero J, Fragoso-Loyo HE, Volpe BT, Diamond B, Huerta PT (2010) Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms. Proc Natl Acad Sci USA 107(43):18569–18574. https://doi.org/10.1073/pnas.1006980107
doi: 10.1073/pnas.1006980107
pubmed: 20921396
pmcid: 2972998
Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H (2019) Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry 90(8):870–881. https://doi.org/10.1136/jnnp-2018-320106
doi: 10.1136/jnnp-2018-320106
pubmed: 30967444
Tjensvoll AB, Lauvsnes MB, Zetterberg H, Kvaloy JT, Kvivik I, Maroni SS, Greve OJ, Beyer MK, Hirohata S, Putterman C, Alves G, Harboe E, Blennow K, Goransson LG, Omdal R (2021) Neurofilament light is a biomarker of brain involvement in lupus and primary Sjogren’s syndrome. J Neurol 268(4):1385–1394. https://doi.org/10.1007/s00415-020-10290-y
doi: 10.1007/s00415-020-10290-y
pubmed: 33128084
Mielke MM, Syrjanen JA, Blennow K, Zetterberg H, Vemuri P, Skoog I, Machulda MM, Kremers WK, Knopman DS, Jack C Jr, Petersen RC, Kern S (2019) Plasma and CSF neurofilament light: relation to longitudinal neuroimaging and cognitive measures. Neurology 93(3):e252–e260. https://doi.org/10.1212/WNL.0000000000007767
doi: 10.1212/WNL.0000000000007767
pubmed: 31182505
pmcid: 6656645
Appenzeller S, Carnevalle AD, Li LM, Costallat LT, Cendes F (2006) Hippocampal atrophy in systemic lupus erythematosus. Ann Rheum Dis 65(12):1585–1589. https://doi.org/10.1136/ard.2005.049486
doi: 10.1136/ard.2005.049486
pubmed: 16439436
pmcid: 1798450
Appenzeller S, Rondina JM, Li LM, Costallat LT, Cendes F (2005) Cerebral and corpus callosum atrophy in systemic lupus erythematosus. Arthritis Rheum 52(9):2783–2789. https://doi.org/10.1002/art.21271
doi: 10.1002/art.21271
pubmed: 16142703
Akamine S, Marutani N, Kanayama D, Gotoh S, Maruyama R, Yanagida K, Sakagami Y, Mori K, Adachi H, Kozawa J, Maeda N, Otsuki M, Matsuoka T, Iwahashi H, Shimomura I, Ikeda M, Kudo T (2020) Renal function is associated with blood neurofilament light chain level in older adults. Sci Rep 10(1):20350. https://doi.org/10.1038/s41598-020-76990-7
doi: 10.1038/s41598-020-76990-7
pubmed: 33230211
pmcid: 7683708
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725. https://doi.org/10.1002/1529-0131(199709)40:9%3c1725::AID-ART29%3e3.0.CO;2-Y
doi: 10.1002/1529-0131(199709)40:9<1725::AID-ART29>3.0.CO;2-Y
pubmed: 9324032
Wechsler D (1955) Manual for the Wechsler Adult Intelligence Scale. Manual for the Wechsler Adult Intelligence Scale. Psychological Corp., Oxford
Wechsler D (1987) WMS-R: Wechsler Memory Scale-revised: manual. Harcourt Brace Jovanovich, New York
Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G (1993) Wisconsin card sorting test manual: revised and expanded. Psychological Assessment Resources Inc, Odessa
Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18:643–662
doi: 10.1037/h0054651
Reitan RM, Wolfson D (1985) The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation. Neuropsychology Press, Tucson
ACR Ad Hoc Committee on Neuropsychiatric Lupus Nomenclature (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42(4):599–608. https://doi.org/10.1002/1529-0131(199904)42:4%3c599::AID-ANR2%3e3.0.CO;2-F
doi: 10.1002/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F
Tibbling G, Link H, Ohman S (1977) Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Investig 37(5):385–390. https://doi.org/10.1080/00365517709091496
doi: 10.1080/00365517709091496
Harboe E, Tjensvoll AB, Maroni S, Goransson LG, Greve OJ, Beyer MK, Herigstad A, Kvaloy JT, Omdal R (2009) Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjogren syndrome: a comparative population-based study. Ann Rheum Dis 68(10):1541–1546. https://doi.org/10.1136/ard.2008.098301
doi: 10.1136/ard.2008.098301
pubmed: 18930990
Lauvsnes MB, Maroni SS, Appenzeller S, Beyer MK, Greve OJ, Kvaloy JT, Harboe E, Goransson LG, Tjensvoll AB, Omdal R (2013) Memory dysfunction in primary Sjogren’s syndrome is associated with anti-NR2 antibodies. Arthritis Rheum 65(12):3209–3217. https://doi.org/10.1002/art.38127
doi: 10.1002/art.38127
pubmed: 23982950
Isshi K, Hirohata S (1996) Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 39(9):1483–1490
doi: 10.1002/art.1780390907
Harboe E, Beyer MK, Greve OJ, Goransson LG, Tjensvoll AB, Kvaloy JT, Omdal R (2009) Cerebral white matter hyperintensities are not increased in patients with primary Sjogren’s syndrome. Eur J Neurol 16(5):576–581. https://doi.org/10.1111/j.1468-1331.2009.02537.x
doi: 10.1111/j.1468-1331.2009.02537.x
pubmed: 19220446
Lauvsnes MB, Beyer MK, Kvaloy JT, Greve OJ, Appenzeller S, Kvivik I, Harboe E, Tjensvoll AB, Goransson LG, Omdal R (2014) Association of hippocampal atrophy with cerebrospinal fluid antibodies against the NR2 subtype of the N-methyl-D-aspartate receptor in patients with systemic lupus erythematosus and patients with primary Sjogren’s syndrome. Arthritis Rheumatol (Hoboken, NJ) 66(12):3387–3394. https://doi.org/10.1002/art.38852
doi: 10.1002/art.38852
Ashburner J, Friston KJ (2000) Voxel-based morphometry–the methods. Neuroimage 11(6 Pt 1):805–821. https://doi.org/10.1006/nimg.2000.0582
doi: 10.1006/nimg.2000.0582
pubmed: 10860804
Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19(3):1233–1239
doi: 10.1016/S1053-8119(03)00169-1
Maldjian JA, Laurienti PJ, Burdette JH (2004) Precentral gyrus discrepancy in electronic versions of the Talairach atlas. Neuroimage 21(1):450–455
doi: 10.1016/j.neuroimage.2003.09.032
Friston KJ, Worsley KJ, Frackowiak RSJ, Mazziotta JC, Evans AC (1993) Assessing the significance of focal activations using their spatial extent. Hum Brain Mapp 1(3):210–220. https://doi.org/10.1002/hbm.460010306
doi: 10.1002/hbm.460010306
Serbruyns L, Gooijers J, Caeyenberghs K, Meesen RL, Cuypers K, Sisti HM, Leemans A, Swinnen SP (2015) Bimanual motor deficits in older adults predicted by diffusion tensor imaging metrics of corpus callosum subregions. Brain Struct Funct 220(1):273–290. https://doi.org/10.1007/s00429-013-0654-z
doi: 10.1007/s00429-013-0654-z
pubmed: 24158531
Pujol-Calderon F, Portelius E, Zetterberg H, Blennow K, Rosengren LE, Hoglund K (2019) Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke. Neurosci Lett 698:58–63. https://doi.org/10.1016/j.neulet.2018.12.042
doi: 10.1016/j.neulet.2018.12.042
pubmed: 30599262
Ainiala H, Loukkola J, Peltola J, Korpela M, Hietaharju A (2001) The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 57(3):496–500
doi: 10.1212/WNL.57.3.496