Serum neurofilament levels in patients with multiple sclerosis: A comparison of SIMOA and high sensitivity ELISA assays and contributing factors to ELISA levels

Revendová, Kamila; Zeman, David; Bunganic, R.; Karasova, K.; Volny, O.; Bar, Michal; Kušnierová, Pavlína

doi:10.1016/j.msard.2022.104177

Cited by 12 publications

(10 citation statements)

References 14 publications

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“…To our knowledge, two other studies have compared methodologies for the quantification of NfL in serum [ 15 , 16 ]. Specifically, ELISA and Simoa were compared in a study by Jens Kuhle et al; however, at the time, the Simoa method was still under development and the ELISA used had an analytical sensitivity of 78.0 pg/mL (as well as being advised to be used with CSF samples, not serum) [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Two Analytical Approaches for the Quantification of Neurofilament Light Chain, a Biomarker of Axonal Damage in Multiple Sclerosis

Pafiti

Krashias

Tzartos

et al. 2023

IJMS

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Neurofilament light chain (NfL), is a neuron-specific cytoskeletal protein detected in extracellular fluid following axonal damage. Extensive research has focused on NfL quantification in CSF, establishing it as a prognostic biomarker of disability progression in Multiple Sclerosis (MS). Our study used a new commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit and Single Molecular Array (Simoa) advanced technology to assess serum NfL levels in MS patients and Healthy Controls (HC). Verifying the most accurate, cost-effective methodology will benefit its application in clinical settings. Blood samples were collected from 54 MS patients and 30 HC. Protocols accompanying the kits were followed. The ELISA thershold was set as 3 S.D. above the mean of the HC. For Simoa, the Z-score calculation created by Jens Kuhle’s group was applied (with permission). Samples exceeding the threshold or z-score ≥1.5 indicated subclinical disease activity. To our knowledge, this is the first study to find strong-positive correlation between ELISA and Simoa for the quantification of NfL in serum (r = 0.919). Despite the strong correlation, Simoa has better analytical sensitivity and can detect small changes in samples making it valuable in clinical settings. Further research is required to evaluate whether serum NfL quantification using ELISA could be utilized to predict disability progression.

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Section: Discussionmentioning

confidence: 99%

A Comparison of Two Analytical Approaches for the Quantification of Neurofilament Light Chain, a Biomarker of Axonal Damage in Multiple Sclerosis

Pafiti

Krashias

Tzartos

et al. 2023

IJMS

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“…Despite promising results, several challenges remain before NfH can be used as a biomarker for MS. For example, NfH levels can fluctuate over time ( Gresle et al, 2014 ) and may be affected by factors such as age, body mass index (BMI), and total blood volume ( Revendova et al, 2022 ). Furthermore, there is currently no standardized method to measure NfH levels, and the different tests achieve inconsistent results ( Gnanapavan et al, 2013a ; Ljubisavljevic et al, 2016 ; Khalil et al, 2018 ; Verberk et al, 2021 ).…”

Section: Potential Biochemical Neurodegeneration Markers Associated W...mentioning

confidence: 99%

Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review

Pogoda-Wesołowska,

Dziedzic,

Maciak

et al. 2023

Front. Mol. Neurosci.

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Approximately 70% of relapsing-remitting multiple sclerosis (RRMS) patients will develop secondary progressive multiple sclerosis (SPMS) within 10–15 years. This progression is characterized by a gradual decline in neurological functionality and increasing limitations of daily activities. Growing evidence suggests that both inflammation and neurodegeneration are associated with various pathological processes throughout the development of MS; therefore, to delay disease progression, it is critical to initiate disease-modifying therapy as soon as it is diagnosed. Currently, a diagnosis of SPMS requires a retrospective assessment of physical disability exacerbation, usually over the previous 6–12 months, which results in a delay of up to 3 years. Hence, there is a need to identify reliable and objective biomarkers for predicting and defining SPMS conversion. This review presents current knowledge of such biomarkers in the context of neurodegeneration associated with MS, and SPMS conversion.

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“…With an increase in neuroprotective or reparative therapeutic strategies, potential therapeutics must be evaluated in EAE through quantitative neuropathology. We applied SIMOA (SIngle MOlecule Array) as this is the emerging ultrasensitive technology based on a bead-conjugate immunocomplex with potential to detect the analytes which are present in ultra-low levels (femtomolar range) and below detection limits for other conventional assays (Cohen et al, 2020; Lasseter et al, 2020; Revendova et al, 2022; Pafiti et al, 2023). It considers an average number of enzymes per bead (AEB) as the unit of measurement.…”

Section: Introductionmentioning

confidence: 99%

Profiling blood-based brain biomarkers and cytokines in experimental autoimmune encephalomyelitis model of multiple sclerosis using single-molecule array technology

Zahoor,

Mir,

Giri

2023

Preprint

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Experimental autoimmune encephalomyelitis (EAE) remains a widely used pre-clinical animal model to study multiple sclerosis (MS). Blood-based cytokines and CNS biomarkers are increasingly used as predictors of neurodegeneration, disease activity, and disability in MS. However, there exists variation in animal model characterization and disease course across animal strains/studies due to understudied confounding factors, limiting the utility of these biomarkers to predict disease activity in EAE. In this study, we investigated the profile of blood-based analytes including, cytokines (IL6, IL17, IL12p70, IL10, and TNFα) and neural markers (NFL and GFAP) in the plasma of relapsing-remitting (RR) (SJL) and chronic (B6) models of EAE during different phases (acute, chronic, and progressive) of disease course using ultrasensitive single molecule array technology (SIMoA, Quanterix), which can detect ultra-low levels of a wide range of analytes. NFL showed a substantial increase during post-disease onset at peak, chronic, and progressive phases in both RR SJL and chronic B6 models of EAE. The increase was markedly pronounced in the chronic B6 model. The leakage of GFAP from CNS into the periphery was also higher after disease onset in EAE, however, it was highest during the acute phase in B6. Out of all cytokines, only IL10 showed consistently lower levels in both models of EAE along the disease duration. We report that NFL, GFAP, and IL10 may be more useful predictors of disease activity and neurological outcome in EAE, which would make them potential candidates for use as surrogate markers for preclinical testing of therapeutic interventions in MS.

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Serum neurofilament levels in patients with multiple sclerosis: A comparison of SIMOA and high sensitivity ELISA assays and contributing factors to ELISA levels

Cited by 12 publications

References 14 publications

A Comparison of Two Analytical Approaches for the Quantification of Neurofilament Light Chain, a Biomarker of Axonal Damage in Multiple Sclerosis

A Comparison of Two Analytical Approaches for the Quantification of Neurofilament Light Chain, a Biomarker of Axonal Damage in Multiple Sclerosis

Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review

Profiling blood-based brain biomarkers and cytokines in experimental autoimmune encephalomyelitis model of multiple sclerosis using single-molecule array technology

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