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神经丝轻链是狼疮和原发性干燥综合征脑受累的生物标志物。

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

机构信息

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

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

出版信息

J Neurol. 2021 Apr;268(4):1385-1394. doi: 10.1007/s00415-020-10290-y. Epub 2020 Oct 30.

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.

摘要

背景

为了验证神经丝轻链(NfL)在脑脊液中是否是系统性红斑狼疮(SLE)和原发性干燥综合征(pSS)患者中枢神经系统受累的生物标志物这一假说,我们测量了 52 例狼疮患者和 54 例 pSS 患者的脑脊液 NfL,并探讨了其与临床、结构、免疫和生化异常的相关性。

方法

我们通过 ELISA 测量了 CSF 中的 NfL、抗-P 抗体、S100B 蛋白和 TWEAK,通过电化学发光法测量了抗-NR2 抗体。在血液中检测了抗磷脂抗体和常规免疫学检查。测量了 CSF 和血清中的 IgG 和白蛋白,以评估血脑屏障功能(Q-白蛋白)和鞘内 IgG 产生(IgG 指数)。进行了脑 MRI 和神经心理学测试。

结果

多变量回归模型显示,SLE 患者脑脊液中抗-NR2 抗体水平的升高与 NfL 水平的升高相关(B 1.27,95%CI 0.88-1.65,p<0.001)。模型中年龄的贡献非常显著(B 0.04,95%CI 0.03-0.05,p<0.001)。在 pSS 组中也观察到了类似的发现。调整年龄和性别后,NfL 水平与任何 MRI 数据之间均无相关性。在 SLE 患者中,较高的 NfL 浓度与运动速度和运动功能受损相关,在 pSS 患者中与运动功能障碍相关。这些相关性在多变量回归模型中仍然存在。

结论

脑脊液中 NfL 浓度的增加是 SLE 和 pSS 患者脑受累的标志物,与抗-NR2 抗体的存在密切相关,并与多个领域的认知障碍相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/7990817/7992f983711b/415_2020_10290_Fig1_HTML.jpg

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