Label‐free analysis of human cerebrospinal fluid addressing various normalization strategies and revealing protein groups affected by multiple sclerosis

Opsahl, Jill A.; Vaudel, Marc; Guldbrandsen, Astrid; Aasebø, Elise; Pesch, Vincent Van; Franciotta, Diego; Myhr, Kjell Morten; Barsnes, Harald; Berle, Magnus; Torkildsen, Øivind; Kroksveen, Ann Cathrine; Berven, Frode S.

doi:10.1002/pmic.201500284

Cited by 29 publications

(32 citation statements)

References 37 publications

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“…Such a protein has yet to be described in tears. A publication of cerebral spinal fluid proteomics indicates that the preferable way to quantify proteins is to first match the samples on total protein amount and then normalize the data based on the median intensities [463]. This technique has yet to be used in tear film biochemistry studies.…”

Section: Biochemical Properties Of Tearsmentioning

confidence: 99%

TFOS DEWS II Tear Film Report

et al. 2017

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The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.

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Section: Biochemical Properties Of Tearsmentioning

confidence: 99%

TFOS DEWS II Tear Film Report

et al. 2017

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“…12 To verify the reproducibility and consistency of the results, all samples were run in duplicate in the same and in 2 consecutive experiments. According to previously published procedures, 15 for each examined patient, the CSF level of each protein was normalized to the total protein concentration of each CSF sample (measured by the Bradford protocol). However, analyses results were unchanged when experiments were also run using absolute concentrations of CSF protein.…”

Section: Study Populationmentioning

confidence: 99%

The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity

Magliozzi

Scalfari

Pisani

et al. 2020

Annals of Neurology

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Objective Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear. Methods We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing‐remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated. Results Forty‐one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C‐index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (β = 4.7*10−4; p < 0.001), TNF (β = 3.1*10−3; p = 0.004), LIGHT (β = 2.6*10−4; p = 0.003), sCD163 (β = 4.3*10−3; p = 0.009), and TWEAK (β = 3.4*10−3; p = 0.024) were associated with more severe cortical thinning. Interpretation A specific CSF profile, mainly characterized by elevated levels of B‐cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562–573

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“… 14 It is upregulated in numerous chronic inflammatory conditions and is expressed by several cells, including microglia, macrophages, and astrocytes. 14 In proteomic studies, 15 , 16 CHI3L1 has been identified as a potential biomarker for MS, and CHI3L1 levels in CSF have been proposed as a prognostic marker for conversion from CIS to MS. 8 , 14 , 17 …”

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confidence: 99%

Neurofilament light chain predicts disease activity in relapsing-remitting MS

Varhaug

Barro

Bjørnevik

et al. 2018

Neurol Neuroimmunol Neuroinflamm

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Objective:To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS).Methods:A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24. Serum samples were collected at baseline and months 3, 6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array assay and CHI3L1 by ELISA and estimated the association with clinical and MRI disease activity using mixed-effects models.Results:NF-L levels were significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3 pg/mL, interquartile range [IQR] 25.9–52.4) and new T2 lesions (37.3 pg/mL, IQR 25.1–48.5) compared with those without (28.0 pg/mL, IQR 21.9–36.4, β = 1.258, p < 0.001 and 27.7 pg/mL, IQR 21.8–35.1, β = 1.251, p < 0.001, respectively). NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.Conclusion:Serum NF-L could be a promising biomarker for subclinical MRI activity and treatment response in RRMS. In clinically stable patients, serum NF-L may offer an alternative to MRI monitoring for subclinical disease activity.ClinicalTrials.gov identifier:NCT00360906.

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Label‐free analysis of human cerebrospinal fluid addressing various normalization strategies and revealing protein groups affected by multiple sclerosis

Cited by 29 publications

References 37 publications

TFOS DEWS II Tear Film Report

TFOS DEWS II Tear Film Report

The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity

Neurofilament light chain predicts disease activity in relapsing-remitting MS

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