期刊
JOURNAL OF NEUROLOGY
卷 268, 期 4, 页码 1385-1394出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-020-10290-y
关键词
Neurofilament light chain; Anti-NR2 antibodies; Cognitive dysfunction; Systemic lupus erythematosus; Primary Sjö grens´ s syndrome
资金
- University of Bergen
- Norwegian Rheumatism Association (Norsk Revmatikerforbund)
- Swedish Research Council [2018-02532, 2017-00915]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Alzheimer Drug Discovery Foundation (ADDF), USA [2018092016862, RDAPB-201809-2016615]
- UK Dementia Research Institute at UCL
- Western Norway Regional Health Authority (WNRHA) [912129, 911807]
- Japan Agency for Medical Research and Development [15eK0410022h0001]
- Norwegian Research Council [287842]
- Norwegian Parkinson Research Foundation
- Reberg's Legacy
- Swedish Alzheimer Foundation [AF-742881]
- Hjarnfonden, Sweden [FO2017-0243]
- Swedish government [ALFGBG-715986]
- Swedish County Councils, the ALF [ALFGBG-715986]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
The study found that increased levels of neurofilament light (NfL) in cerebrospinal fluid are associated with cerebral involvement in patients with systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS), strongly correlated with the presence of anti-NR2 antibodies, and related to cognitive impairment in multiple 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 Sjogren'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.
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