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

Anne B Tjensvoll, Maria B Lauvsnes, Henrik Zetterberg, Jan T Kvaløy, Ingeborg Kvivik, Stian S Maroni, Ole J Greve, Mona K Beyer, Shunsei Hirohata, Chaim Putterman, Guido Alves, Erna Harboe, Kaj Blennow, Lasse G Gøransson, Roald Omdal, Anne B Tjensvoll, Maria B Lauvsnes, Henrik Zetterberg, Jan T Kvaløy, Ingeborg Kvivik, Stian S Maroni, Ole J Greve, Mona K Beyer, Shunsei Hirohata, Chaim Putterman, Guido Alves, Erna Harboe, Kaj Blennow, Lasse G Gøransson, Roald Omdal

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.

Keywords: Anti-NR2 antibodies; Cognitive dysfunction; Neurofilament light chain; Primary Sjögrens´s syndrome; Systemic lupus erythematosus.

Conflict of interest statement

Dr. Henrik Zetterberg reports that he served on scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure, and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. Dr. Mona Beyer has received honoraria for lecturing, from Novartis and Biogen Idec, Merck AB, Roche Norge, and Sanofi Genzyme. Dr. Kaj Blennow has served as a consultant or on advisory boards for Abcam, Axon, Biogen, Lilly, MagQu, Novartis, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. Dr. Roald Omdal has received speaker honoraria from several pharmaceutical companies. The other authors report no conflicts of interest.

Figures

Fig. 1
Fig. 1
Neuron with neurofilaments. Figure illustrates disintegrating neurofilaments, and neurofilament light chains (NfL) leaking out of the axon. Figure created with BioRender.com
Fig. 2
Fig. 2
Influence of age on CSF NfL concentration. Results are shown for patients with (a) systemic lupus erythematosus (N = 47) and (b) primary Sjögren’s syndrome (N = 49)
Fig. 3
Fig. 3
Associations between NfL and anti-NR2 antibodies in CSF. Results are shown for patients with (a) systemic lupus erythematosus (N = 47) and (b) primary Sjögren’s syndrome (N = 49)

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Source: PubMed

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