The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

Lycke, Jan; Zetterberg, Henrik

doi:10.1080/1744666x.2017.1400380

Cited by 22 publications

(19 citation statements)

References 113 publications

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“…The presence of these metabolic markers not only in CSF but also in an easily accessible body fluid like blood suggests a potential role of these molecules as biomarkers for disease activity and progression in course of MS. Thus, as was the case for other biomarkers [40], further studies are warranted to validate the use of these promising molecules, in particular (i) on patients presenting clinically isolated syndromes and on healthy controls to evaluate the capability to guide an early diagnosis of MS, and (ii) during immunomodulating treatment for the monitoring of disease activity and progression.…”

Section: Discussionmentioning

confidence: 99%

Correlation between auto/mitophagic processes and magnetic resonance imaging activity in multiple sclerosis patients

Castellazzi

Patergnani

Donadio

et al. 2019

J Neuroinflammation

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Background An alteration of autophagy and mitophagy, two highly conserved lysosome-dependent degradation pathways involved in the maintenance of cellular homeostasis, has been associated with multiple sclerosis (MS). Objective To search the level of autophagy-related 5 (ATG5) and Parkin proteins, as markers of autophagy and mitophagy respectively, and lactate in a cohort of MS patients. Methods Cerebrospinal fluid (CSF) and serum samples from 60 MS patients were analyzed: 30 with magnetic resonance imaging (MRI) evidence of disease activity, gadolinium (Gd)-based contrast agent positive (Gd+), and 30 without MRI evidence of disease activity (Gd−). ATG5, Parkin, and lactate were measured using commercially available products. Results and conclusions Serum levels of ATG5, Parkin, and lactate were more elevated in Gd+ than in Gd− MS patients ( p < 0.0001), and CSF concentrations of ATG5 and Parkin were greater in Gd+ than in Gd− MS ( p < 0.0001). Our results demonstrated that molecular markers of autophagy and mitophagy are increased in CSF of MS patients during the active phases of the disease and that these catabolic markers, together with lactate, are also remarkably augmented in blood suggesting a role of these processes in MS pathogenesis and the possible use of these molecules as biomarkers of disease activity.

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Section: Discussionmentioning

confidence: 99%

Correlation between auto/mitophagic processes and magnetic resonance imaging activity in multiple sclerosis patients

Castellazzi

Patergnani

Donadio

et al. 2019

J Neuroinflammation

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“…Neurofilament light chain (NfL) is a component of the neuronal cytoskeleton and is released into the cerebrospinal fluid (CSF) and blood after neuronal-axonal injury (10,11). Serum NfL (sNfL) measured via ultra-sensitive single-molecule arrays (SIMOA) has been observed to be increased in multiple neurological diseases-including neurodegenerative disorders, trauma, and multiple sclerosis (MS)-and strongly correlates with CSF NfL (12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies

et al. 2021

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Objective: To evaluate the potential of serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP) as disease biomarkers in neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-ab) or myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD).Methods: Patients with AQP4-ab-positive NMOSD (n = 51), MOGAD (n = 42), and relapsing-remitting multiple sclerosis (RRMS) (n = 31 for sNfL and n = 22 for sGFAP testing), as well as healthy controls (HCs) (n = 28), were enrolled prospectively. We assessed sNfL and sGFAP levels using ultrasensitive single-molecule array assays. Correlations of sNfL and sGFAP levels with clinical parameters were further examined in AQP4-ab-positive NMOSD and MOGAD patients.Results: sNfL levels were significantly higher in patients with AQP4-ab-positive NMOSD (median 17.6 pg/mL), MOGAD (27.2 pg/mL), and RRMS (24.5 pg/mL) than in HCs (7.4 pg/mL, all p < 0.001). sGFAP levels were remarkably increased in patients with AQP4-ab-positive NMOSD (274.1 pg/mL) and MOGAD (136.7 pg/mL) than in HCs (61.4 pg/mL, both p < 0.001). Besides, sGFAP levels were also significantly higher in patients with AQP4-ab-positive NMOSD compared to those in RRMS patients (66.5 pg/mL, p < 0.001). The sGFAP/sNfL ratio exhibited good discrimination among the three disease groups. sNfL levels increased during relapse in patients with MOGAD (p = 0.049) and RRMS (p < 0.001), while sGFAP levels increased during relapse in all three of the disease groups (all p < 0.05). Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale scores in AQP4-ab-positive NMOSD (β = 1.88, p = 0.018 and β = 2.04, p = 0.032) and MOGAD patients (β = 1.98, p = 0.013 and β = 1.52, p = 0.008).Conclusion: sNfL and sGFAP levels are associated with disease severity in AQP4-ab-positive NMOSD and MOGAD patients, and the sGFAP/sNfL ratio may reflect distinct disease pathogenesis.

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“…Multiple sclerosis is believed to be driven by systemic immune activation of autoimmunity against CNS components (4,5), where encephalitogenic cells accumulate in the target organ (6,7). Due to the proximity to the CNS, cerebrospinal fluid (CSF) has been the primary object of biomarker exploration (8,9). Immunoglobulin G (IgG) index and detection of oligoclonal bands are currently used to support diagnosis (10).…”

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confidence: 99%

Inflammation-related plasma and CSF biomarkers for multiple sclerosis

Huang

Khademi

Fugger

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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120

110

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Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF< 4 × 10−5,Pplasma< 4 × 10−5), and plasma CCL20 was associated with disease severity (P= 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

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The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

Cited by 22 publications

References 113 publications

Correlation between auto/mitophagic processes and magnetic resonance imaging activity in multiple sclerosis patients

Correlation between auto/mitophagic processes and magnetic resonance imaging activity in multiple sclerosis patients

Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies

Inflammation-related plasma and CSF biomarkers for multiple sclerosis

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