Abstract
BackgroundTo 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.MethodsIn 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.ResultsA 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.ConclusionsIncreased 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.
Highlights
Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease that frequently involves the CNS [1]
The main finding in this study was that increasing concentrations of neurofilament light (NfL) in CSF was associated with increasing levels of anti-NR2 antibodies in CSF, and was a marker of cognitive dysfunction in patients with systemic lupus erythematosus (SLE) as well as in primary Sjögren’s syndrome (pSS)
We investigated a panel of other biomarkers for brain involvement, and several associations between NfL and these biomarkers were evident, antiNR2 antibodies was the dominating actor with a strong and consistent association to NfL levels evident both in univariate and multivariate models
Summary
Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease that frequently involves the CNS [1]. We hypothesized that NfL levels in CSF would be increased in patients with SLE and/or pSS. 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 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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