Neurofilament light is a biomarker of brain involvement in lupus and primary Sjögren's syndrome.

Biomarkers Brain / diagnostic imaging Humans Intermediate Filaments Lupus Erythematosus, Systemic / complications Neurofilament Proteins Sjogren's Syndrome / complications
Anti-NR2 antibodies Cognitive dysfunction Neurofilament light chain Primary Sjögrens´s syndrome 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:
Apr 2021
Historique:
received: 09 07 2020
accepted: 20 10 2020
revised: 20 10 2020
pubmed: 1 11 2020
medline: 22 6 2021
entrez: 31 10 2020
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

DOI: 10.1007/s00415-020-10290-y PMID: 33128084 PMC: PMC7990817
pubmed: 33128084
doi: 10.1007/s00415-020-10290-y
pii: 10.1007/s00415-020-10290-y
pmc: PMC7990817
doi:

Substances chimiques

Biomarkers 0
Neurofilament Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1385-1394

Subventions

Organisme : Helse Vest Regionalt Helseføretak
ID : 911807

Références

Schwartz N, Stock AD, Putterman C (2019) Neuropsychiatric lupus: new mechanistic insights and future treatment directions. Nat Rev Rheumatol 15(3):137–152. https://doi.org/10.1038/s41584-018-0156-8
doi: 10.1038/s41584-018-0156-8 pubmed: 30659245
Mariette X, Criswell LA (2018) Primary Sjogren’s syndrome. N Engl J Med 378(10):931–939. https://doi.org/10.1056/NEJMcp1702514
doi: 10.1056/NEJMcp1702514 pubmed: 29514034
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
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
Hanly JG, Hong C, Smith S, Fisk JD (1999) A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 42(4):728–734. https://doi.org/10.1002/1529-0131(199904)42:4%3c728::AID-ANR16%3e3.0.CO;2-O
doi: 10.1002/1529-0131(199904)42:4<728::AID-ANR16>3.0.CO;2-O pubmed: 10211887
Magro-Checa C, Kumar S, Ramiro S, Beaart-van de Voorde LJ, Eikenboom J, Ronen I, de Bresser J, van Buchem MA, Huizinga TW, Steup-Beekman GM (2019) Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort. Lupus 28(1):94–103. https://doi.org/10.1177/0961203318816819
doi: 10.1177/0961203318816819 pubmed: 30526327
Omdal R, Brokstad K, Waterloo K, Koldingsnes W, Jonsson R, Mellgren SI (2005) Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol 12(5):392–398. https://doi.org/10.1111/j.1468-1331.2004.00976.x
doi: 10.1111/j.1468-1331.2004.00976.x pubmed: 15804272
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
Viana VT, Durcan L, Bonfa E, Elkon KB (2017) Ribosomal P antibody: 30 years on the road. Lupus 26(5):453–462. https://doi.org/10.1177/0961203317690243
doi: 10.1177/0961203317690243 pubmed: 28394227
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
Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH (2002) Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61(6):554–558
doi: 10.1136/ard.61.6.554
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 35 (6):630–640
Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, Bacon P, Bombardieri S, Hanly J, Hay E, Isenberg D, Jones J, Kalunian K, Maddison P, Nived O, Petri M, Richter M, Sanchez-Guerrero J, Snaith M, Sturfelt G, Symmons D, Zoma A (1996) The development and initial validation of the systemic lupus international collaborating Clinics/American college of rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39(3):363–369
doi: 10.1002/art.1780390303
The International Classification of Headache Disorders: 2nd edition (2004). Cephalalgia 24(Suppl 1_:9–160. doi:10.1111/j.1468-2982.2003.00824.x
Beck AT, Beamesderfer A (1974) Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatry 7:151–169
doi: 10.1159/000395074
Wolfe F (2004) Fatigue assessments in rheumatoid arthritis: comparative performance of visual analog scales and longer fatigue questionnaires in 7760 patients. J Rheumatol 31(10):1896–1902
pubmed: 15468350
Tibbling G, Link H, Ohman S (1977) Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scandinavian J Clin Laboratory Investigation 37(5):385–390. https://doi.org/10.1080/00365517709091496
doi: 10.1080/00365517709091496
Hirohata S, Arinuma Y, Takayama M, Yoshio T (2007) Association of cerebrospinal fluid anti-ribosomal p protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther 9(3):R44. https://doi.org/10.1186/ar2184
doi: 10.1186/ar2184 pubmed: 17472755 pmcid: 2206358
Lauvsnes MB, Tjensvoll AB, Maroni SS, Kvivik I, Grimstad T, Greve OJ, Harboe E, Goransson LG, Putterman C, Omdal R (2018) The blood-brain barrier, TWEAK, and neuropsychiatric involvement in human systemic lupus erythematosus and primary Sjogren’s syndrome. Lupus 27(13):2101–2111. https://doi.org/10.1177/0961203318804895
doi: 10.1177/0961203318804895 pubmed: 30282561
Scheltens P, Barkhof F, Leys D, Pruvo JP, Nauta JJ, Vermersch P, Steinling M, Valk J (1993) A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci 114(1):7–12
doi: 10.1016/0022-510X(93)90041-V
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 & rheumatology (Hoboken, NJ) 66(12):3387–3394. https://doi.org/10.1002/art.38852
doi: 10.1002/art.38852
Wechsler D (1987) WMS-R: Wechsler Memory Scale-Revised : Manual. Harcourt Brace Jovanovich
Wechsler D (1955) Manual for the Wechsler Adult Intelligence Scale. Manual for the Wechsler Adult Intelligence Scale. Psychological Corp., Oxford, England
Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18:643–662
doi: 10.1037/h0054651
Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G (1993) Wisconsin card sorting test manual: revised and expanded. Psychological Assessment Resources Inc, Odessa
Benton AL, Hamsher K (1977) Multilingual aphasia examination. University of Iowa
Reitan RM, Wolfson D (1985) The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation. Neuropsychology Press
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
Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J (2018) Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 14(10):577–589. https://doi.org/10.1038/s41582-018-0058-z
doi: 10.1038/s41582-018-0058-z pubmed: 30171200
Trysberg E, Nylen K, Rosengren LE, Tarkowski A (2003) Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement. Arthritis Rheum 48(10):2881–2887. https://doi.org/10.1002/art.11279
doi: 10.1002/art.11279 pubmed: 14558094
Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97(7):889–901. https://doi.org/10.1016/s0092-8674(00)80801-6
doi: 10.1016/s0092-8674(00)80801-6 pubmed: 10399917
Bertheloot D, Latz E (2017) HMGB1, IL-1alpha, IL-33 and S100 proteins: dual-function alarmins. Cell Mol Immunol 14(1):43–64. https://doi.org/10.1038/cmi.2016.34
doi: 10.1038/cmi.2016.34 pubmed: 27569562
Chi JM, Mackay M, Hoang A, Cheng K, Aranow C, Ivanidze J, Volpe B, Diamond B, Sanelli PC (2019) Alterations in blood-brain barrier permeability in patients with systemic lupus erythematosus. AJNR Am J Neuroradiol 40(3):470–477. https://doi.org/10.3174/ajnr.A5990
doi: 10.3174/ajnr.A5990 pubmed: 30792254 pmcid: 6483727
Gulati G, Iffland PH 2nd, Janigro D, Zhang B, Luggen ME (2016) Anti-NR2 antibodies, blood-brain barrier, and cognitive dysfunction. Clin Rheumatol 35(12):2989–2997. https://doi.org/10.1007/s10067-016-3339-1
doi: 10.1007/s10067-016-3339-1 pubmed: 27357716
Polavarapu R, Gongora MC, Winkles JA, Yepes M (2005) Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-kappa B pathway activation. J Neurosci 25(44):10094–10100. https://doi.org/10.1523/jneurosci.3382-05.2005
doi: 10.1523/jneurosci.3382-05.2005 pubmed: 16267216 pmcid: 6725778
Yepes M (2007) Tweak and FN14 in central nervous system health and disease. Front Biosci 12:2772–2781
doi: 10.2741/2271
Fragoso-Loyo H, Atisha-Fregoso Y, Nunez-Alvarez CA, Llorente L (2016) Utility of TWEAK to assess neuropsychiatric disease activity in systemic lupus erhytematosus. Lupus 25(4):364–369. https://doi.org/10.1177/0961203315610206
doi: 10.1177/0961203315610206 pubmed: 26466614

Auteurs

Anne B Tjensvoll (AB)

Department of Neurology, Stavanger University Hospital, Stavanger, Norway.

Maria B Lauvsnes (MB)

Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway.

Henrik Zetterberg (H)

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At the University of Gothenburg, Mölndal, Sweden.
UK Dementia Research Institute At UCL, London, UK.
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.

Jan T Kvaløy (JT)

Research Department, Stavanger University Hospital, Stavanger, Norway.
Department of Mathematics and Physics, University of Stavanger, Stavanger, Norway.

Ingeborg Kvivik (I)

Research Department, Stavanger University Hospital, Stavanger, Norway.

Stian S Maroni (SS)

Clinical Neuropsychology Unit, Division of Psychiatry, Stavanger University Hospital, Stavanger, Norway.

Ole J Greve (OJ)

Department of Radiology, Stavanger University Hospital, Stavanger, Norway.

Mona K Beyer (MK)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.

Shunsei Hirohata (S)

Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, 252-0374, Japan.

Chaim Putterman (C)

Division of Rheumatology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
Azrieli School of Medicine Bar-Ilan University, Zefat, Israel.
Galilee Medical Center Research Institute, Nahariya, Israel.

Guido Alves (G)

The Norwegian Centre for Movement Disorders and Department of Neurology, Stavanger University Hospital, Stavanger, Norway.
Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.

Erna Harboe (E)

Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway.

Kaj Blennow (K)

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At the University of Gothenburg, Mölndal, Sweden.

Lasse G Gøransson (LG)

Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway.
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.

Roald Omdal (R)

Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway. roald.omdal@lyse.net.
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway. roald.omdal@lyse.net.
ORCID: 0000-0002-6051-4658

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Neurofilament light is a biomarker of brain...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Neurofilament light is a biomarker of brain...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Neurofilament light is a biomarker of brain...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Cytosquelette › Filaments intermédiaires › Neurofilament light is a biomarker of brain...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Lupus érythémateux disséminé › Neurofilament light is a biomarker of brain...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines neurofilamenteuses › Neurofilament light is a biomarker of brain...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Polyarthrite rhumatoïde › Syndrome de Gougerot-Sjögren › Neurofilament light is a biomarker of brain...