Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis

2013 ◽  
Vol 19 (11) ◽  
pp. 1462-1472 ◽  
Author(s):  
Violaine K Harris ◽  
Nicola Donelan ◽  
Qi Jiang Yan ◽  
Kristi Clark ◽  
Amir Touray ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Brain Tissue ◽  
Disease Process ◽  
Autoimmune Encephalomyelitis ◽  
Fetuin A ◽  
Potential Biomarker ◽  
One Year ◽  
Deficient Mice

Background: There is an urgent need for biomarkers in multiple sclerosis (MS) that can reliably measure ongoing disease activity relative to inflammation, neurodegeneration, and demyelination/remyelination. Fetuin-A was recently identified as a potential biomarker in MS cerebrospinal fluid (CSF). Fetuin-A has diverse functions, including a role in immune pathways. Objective: The objective of this research is to investigate whether fetuin-A is a direct indicator of disease activity. Methods: We measured fetuin-A in CSF and plasma of patients with MS and correlated these findings to clinical disease activity and natalizumab response. Fetuin-A expression was characterized in MS brain tissue and in experimental autoimmune encephalomyelitis (EAE) mice. We also examined the pathogenic role of fetuin-A in EAE using fetuin-A-deficient mice. Results: Elevated CSF fetuin-A correlated with disease activity in MS. In natalizumab-treated patients, CSF fetuin-A levels were reduced one year post-treatment, correlating with therapeutic response. Fetuin-A was markedly elevated in demyelinated lesions and in gray matter within MS brain tissue. Similarly, fetuin-A was elevated in degenerating neurons around demyelinated lesions in EAE. Fetuin-A-deficient mice demonstrated delayed onset and reduced severity of EAE symptoms. Conclusions: Our results show that CSF fetuin-A is a biomarker of disease activity and natalizumab response in MS. Neuronal expression of fetuin-A suggests that fetuin-A may play a pathological role in the disease process.

scholarly journals Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0163802 ◽  
Author(s):  
Deepak K. Kaushik ◽  
Heather Y. F. Yong ◽  
Jennifer N. Hahn ◽  
Claudia Silva ◽  
Steven Casha ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity

scholarly journals CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD

2020 ◽  
Vol 91 (6) ◽  
pp. 605-611
Author(s):  
Iris Kleerekooper ◽  
Megan K Herbert ◽  
H Bea Kuiperij ◽  
Douglas Kazutoshi Sato ◽  
Kazuo Fujihara ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Glutamine Synthetase ◽  
Glial Fibrillary Acidic Protein ◽  
Optic Neuritis ◽  
Disease Activity ◽  
Similar Pattern ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Csf Levels

ObjectiveTo explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis.MethodsCerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37).ResultsGFAP and GS concentrations differed significantly across groups (both p<0.001), showing a similar pattern of elevation in patients with AQP4-Ab-seropositive NMOSD. GS and GFAP were significantly correlated, particularly in patients with AQP4-Ab-seropositive NMOSD (rs=0.70, p<0.001). Interestingly, GFAP levels in some patients with double-Ab-seronegative NMOSD were markedly increased.ConclusionsOur data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.

scholarly journals IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis

2020 ◽  
Vol 14 ◽  
Author(s):  
Mario Stampanoni Bassi ◽  
Ennio Iezzi ◽  
Jelena Drulovic ◽  
Tatjana Pekmezovic ◽  
Luana Gilio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity

Quantitative Cerebrospinal Fluid IgG Measurements as a Marker of Disease Activity in Multiple Sclerosis

1986 ◽  
Vol 43 (11) ◽  
pp. 1129-1131 ◽  
Author(s):  
J. T. Caroscio ◽  
S. Kochwa ◽  
H. Sacks ◽  
S. Makuku ◽  
J. A. Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity

Protein biomarkers for multiple sclerosis: semi-quantitative analysis of cerebrospinal fluid candidate protein biomarkers in different forms of multiple sclerosis

2012 ◽  
Vol 18 (8) ◽  
pp. 1081-1091 ◽  
Author(s):  
Timucin Avsar ◽  
Didem Korkmaz ◽  
Melih Tütüncü ◽  
N Onat Demirci ◽  
Sabahattin Saip ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Process ◽  
Underlying Disease ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Protein Levels ◽  
Clinical Subtype

Background: The complex pathogenesis of multiple sclerosis, combined with an unpredictable prognosis, requires identification of disease-specific diagnostic and prognostic biomarkers. Objective: To determine whether inflammatory proteins, such as neurofilament light chain, myelin oligodendrocyte glycoprotein and myelin basic protein, and neurodegenerative proteins, such as tau and glial fibrillary acidic protein, can serve as biomarkers for predicting the clinical subtype and prognosis of MS. Methods: Cerebrospinal fluid and serum samples were collected from patients with a diagnosis of clinically isolated syndrome ( n = 46), relapsing–remitting MS ( n = 67) or primary-progressive MS ( n = 22) along with controls having other non-inflammatory neurological disease ( n = 22). Western blot analyses were performed for the listed proteins. Protein levels were compared among different clinical subtypes using one-way analysis of variance analysis. The k-nearest neighbour algorithm was further used to assess the predictive use of these proteins for clinical subtype classification. Results: The results showed that each of tau, GFAP, MOG and NFL protein concentrations differed significantly ( p < 0.001) in multiple sclerosis clinical subtypes compared with the controls. Levels of the proteins also differed between the multiple sclerosis clinical subtypes, which may be associated with the underlying disease process. Classification studies revealed that these proteins might be useful for identifying multiple sclerosis clinical subtypes. Conclusions: We showed that select biomarkers may have potential in identifying multiple sclerosis clinical subtypes. We also showed that the predictive value of the prognosis increased when using a combination of the proteins versus using them individually.

scholarly journals Affinity Proteomic Profiling of Plasma, Cerebrospinal Fluid, and Brain Tissue within Multiple Sclerosis

2014 ◽  
Vol 13 (11) ◽  
pp. 4607-4619 ◽  
Author(s):  
Sanna Byström ◽  
Burcu Ayoglu ◽  
Anna Häggmark ◽  
Nicholas Mitsios ◽  
Mun-Gwan Hong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Brain Tissue ◽  
Proteomic Profiling

Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis

2010 ◽  
Vol 17 (1) ◽  
pp. 32-42 ◽  
Author(s):  
Lars Börnsen ◽  
Mohsen Khademi ◽  
Tomas Olsson ◽  
Per Soelberg Sørensen ◽  
Finn Sellebjerg
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cross Sectional ◽  
Blood Samples ◽  
Relapsing Remitting ◽  
Repeated Sampling ◽  
Csf Levels

Background:The cytokine osteopontin (OPN) is a potential key player in the immunopathogenesis of multiple sclerosis (MS) and a candidate biomarker for disease activity. Objective:The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid (CSF) across the clinical spectrum of MS. Methods:Our research consisted of a cross-sectional study of patients from two randomized, placebo-controlled trials. Concentrations of OPN and other blood and CSF markers were determined using an enzyme-linked immunosorbent assay (ELISA). Samples were obtained from untreated patients with exacerbation of clinically isolated syndrome (CIS) ( n = 25) and relapsing–remitting MS (RRMS) ( n = 41) of whom 48 participated in clinical trials, randomly allocated to treatment with placebo or methylprednisolone (MP) and undergoing repeated sampling after 3 weeks. Furthermore, we obtained CSF and blood samples from patients with primary progressive MS (PPMS, n = 9), secondary progressive MS (SPMS, n = 28) and other neurological disorders (OND, n = 44), and blood samples from 24 healthy subjects. Results:OPN concentrations were significantly increased in the CSF of patients with CIS ( p = 0.02) and RRMS ( p < 0.001) in exacerbation compared to patients with OND, and increased levels of OPN were associated with high values of other biomarkers of inflammation. At 3-week follow-up CSF OPN concentrations had decreased significantly from baseline regardless treatment with placebo or MP. Patients with PPMS had increased OPN levels in the CSF ( p = 0.004) and high CSF levels of OPN were associated with high degrees of disability. Conclusions:OPN concentration in the CSF is a dynamic indicator of disease activity in RRMS, presumably reflecting ongoing inflammation. Increased CSF OPN concentrations in PPMS may indicate ongoing inflammation even in these patients.

Reduction of angiotensin II in the cerebrospinal fluid of patients with multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 557-560 ◽  
Author(s):  
M Kawajiri ◽  
M Mogi ◽  
M Osoegawa ◽  
T Matsuoka ◽  
K Tsukuda ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Angiotensin Ii ◽  
Neurological Diseases ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Disability Status ◽  
Scale Scores ◽  
Inflammatory Neuropathies ◽  
And Control

We previously demonstrated that angiotensin II acts as a crucial neuroprotective factor after neural injury through angiotensin II type-2 (AT2) receptor signaling. Although the pathway is known to play an important role in the development of experimental autoimmune encephalomyelitis, cerebrospinal fluid (CSF) angiotensin II levels in patients with multiple sclerosis (MS) have never been studied. To clarify the significance of angiotensin II in MS, we assayed angiotensin II concentrations using an established enzyme-linked immunoabsorbent assay in CSF samples from patients with MS ( n = 21), patients with inflammatory neuropathies (IN) ( n = 23) and control individuals who did not have either of the neurological diseases or any other disease that might affect the angiotensin II levels in the CSF (control) ( n = 24). Angiotensin II levels in the CSF were 3.79 ± 1.54 pg/ml in the MS group, 5.13 ± 2.27 pg/ml in the IN group and 6.71 ± 2.65 pg/ml in the control group. The angiotensin II levels in the CSF of the MS group were significantly lower than in the control group ( p = 0.00057). Angiotensin II concentration in the CSF tended to have a negative correlation with the Kurtzke’s Expanded Disability Status Scale scores during MS relapse ( p = 0.0847). These findings suggest that reduced levels of intrathecal angiotensin II may be related to the abnormal neural damage and repair processes in MS.

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