Chitinase 3-like 1 is not a target antigen in patients with multiple sclerosis

2020 ◽  
pp. 135245852098014
Author(s):  
Manuel Comabella ◽  
Claudia Deutschmann ◽  
Luciana Midaglia ◽  
Peter Schierack ◽  
Júlia Martínez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immunosorbent Assay ◽  
Prognostic Biomarker ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Healthy Controls ◽  
Secondary Progressive ◽  
Inflammatory Conditions ◽  
Relapsing Remitting ◽  
Ms Pathogenesis

Autoimmunity to chitinase 3-like 1 (CHI3L1) has recently been reported in hepatic and bowel inflammatory conditions. Considering that CHI3L1 plays a role as prognostic biomarker in multiple sclerosis (MS), here we investigated CHI3L1 as potential autoantigenic target in the disease. We determined serum CHI3L1 autoantibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 60 untreated MS patients with different clinical forms of the disease and 20 healthy controls (HC). IgG levels to CHI3L1 were similar between patients with relapsing-remitting MS, primary and secondary progressive MS, and HC. These findings do not support a role for CHI3L1 autoantibodies in MS pathogenesis.

Chitinase 3-like 1 plasma levels are increased in patients with progressive forms of multiple sclerosis

2011 ◽  
Vol 18 (7) ◽  
pp. 983-990 ◽  
Author(s):  
E Cantó ◽  
F Reverter ◽  
C Morcillo-Suárez ◽  
F Matesanz ◽  
O Fernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Clinical Course ◽  
Healthy Controls ◽  
Protein Levels ◽  
Secondary Progressive ◽  
Inflammatory Conditions ◽  
Relapsing Remitting ◽  
Ms Pathogenesis

Background: Chitinase 3-like 1 (CHI3L1) is upregulated in a wide variety of inflammatory conditions. Recent studies have pointed to a role of CHI3L1 in multiple sclerosis (MS) pathogenesis. Objective: The objective of this study was to investigate the role of plasma CHI3L1 in MS clinical course and disease activity and to evaluate the effect of interferon-beta (IFNβ) treatment on protein levels. Methods: Plasma CHI3L1 levels were determined by ELISA in 57 healthy controls (HC), 220 untreated MS patients [66 primary progressive MS patients (PPMS), 30 secondary progressive MS patients (SPMS), and 124 relapsing–remitting MS patients (RRMS), 94 during clinical remission and 30 during relapse], and 32 MS patients receiving IFNβ treatment. A polymorphism of the CHI3L1 gene, rs4950928, was genotyped in 3274 MS patients and 3483 HC. Results: Plasma CHI3L1 levels were significantly increased in patients with progressive forms of MS compared with RRMS patients and HC. CHI3L1 levels were similar between RRMS patients in relapse and remission. A trend towards decreased CHI3L1 levels was observed in IFNβ-treated patients. Allele C of rs4950928 was significantly associated with PPMS patients and with higher plasma CHI3L1 levels. Conclusions: These findings point to a role of CHI3L1 in patients with progressive forms of MS, particularly in those with PPMS.

Lack of confirmation of anti-inward rectifying potassium channel 4.1 antibodies as reliable markers of multiple sclerosis

2014 ◽  
Vol 20 (13) ◽  
pp. 1699-1703 ◽  
Author(s):  
Elodie Nerrant ◽  
Céline Salsac ◽  
Mahmoud Charif ◽  
Xavier Ayrignac ◽  
Clarisse Carra-Dalliere ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Potassium Channel ◽  
Immunosorbent Assay ◽  
Neurological Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Lower Prevalence ◽  
Immunofluorescence Analysis ◽  
Specific Staining ◽  
Inward Rectifying Potassium Channel

Background: auto-antibodies against the potassium channel inward rectifying potassium channel 4.1 (Kir4.1) have previously been identified in 46% of patients with multiple sclerosis (MS). Objectives: to confirm these findings. Methods: we evaluated the presence of anti-Kir4.1 antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence in 268 MS patients, 46 patients with other neurological diseases (OND) and 45 healthy controls. Results: anti-Kir4.1 antibodies were found in 7.5% of MS patients, 4.3% of OND patients and 4.4% of healthy controls. Immunofluorescence analysis did not identify any specific staining. Conclusions: we confirmed the presence of anti-Kir4.1 antibodies in MS patients, but at a much lower prevalence than previously reported.

scholarly journals Differentiation of relapsing-remitting and secondary progressive multiple sclerosis: a magnetic resonance spectroscopy study based on machine learning

2020 ◽  
Vol 78 (12) ◽  
pp. 789-796
Author(s):  
Ziya EKŞİ ◽  
Murat ÇAKIROĞLU ◽  
Cemil ÖZ ◽  
Ayse ARALAŞMAK ◽  
Hasan Hüseyin KARADELİ ◽  
...  
Keyword(s):  
Machine Learning ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Mr Spectroscopy ◽  
Support Vector ◽  
Resonance Spectroscopy ◽  
Healthy Controls ◽  
Magnetic Resonance Spectroscopy Study ◽  
Secondary Progressive ◽  
Relapsing Remitting

ABSTRACT Introduction: Magnetic resonance imaging (MRI) is the most important tool for diagnosis and follow-up in multiple sclerosis (MS). The discrimination of relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS) is clinically difficult, and developing the proposal presented in this study would contribute to the process. Objective: This study aimed to ensure the automatic classification of healthy controls, RRMS, and SPMS by using MR spectroscopy and machine learning methods. Methods: MR spectroscopy (MRS) was performed on a total of 91 participants, distributed into healthy controls (n=30), RRMS (n=36), and SPMS (n=25). Firstly, MRS metabolites were identified using signal processing techniques. Secondly, feature extraction was performed based on MRS Spectra. N-acetylaspartate (NAA) was the most significant metabolite in differentiating MS types. Lastly, binary classifications (healthy controls-RRMS and RRMS-SPMS) were carried out according to features obtained by the Support Vector Machine algorithm. Results: RRMS cases were differentiated from healthy controls with 85% accuracy, 90.91% sensitivity, and 77.78% specificity. RRMS and SPMS were classified with 83.33% accuracy, 81.81% sensitivity, and 85.71% specificity. Conclusions: A combined analysis of MRS and computer-aided diagnosis may be useful as a complementary imaging technique to determine MS types.

scholarly journals Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
L. Messinis ◽  
M. H. Kosmidis ◽  
C. Vlahou ◽  
A. C. Malegiannaki ◽  
G. Gatzounis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Verbal Fluency ◽  
Progressive Multiple Sclerosis ◽  
Word Production ◽  
Secondary Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Fluency Task

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

scholarly journals Cerebrospinal fluid growth-associated protein 43 in multiple sclerosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Åsa Sandelius ◽  
Sofia Sandgren ◽  
Markus Axelsson ◽  
Clas Malmeström ◽  
Lenka Novakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Highly Active ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying

AbstractNeurodegeneration in multiple sclerosis (MS) correlates with disease progression and reparative processes may be triggered. Growth-associated protein 43 (GAP-43) exhibits induced expression during axonal growth and reduced expression during MS progression. We aimed to evaluate if GAP-43 can serve as a biomarker of regeneration in relapsing-remitting MS (RRMS) and whether disease-modifying therapies (DMTs) influence GAP-43 concentration in cerebrospinal fluid (CSF). GAP-43 was measured using an enzyme-linked immunosorbent assay in 105 MS patients (73 RRMS, 12 primary progressive MS, 20 secondary progressive MS) and 23 healthy controls (HCs). In 35 of the patients, lumbar puncture, clinical assessment, and magnetic resonance imaging was performed before initiation of therapeutic intervention, and at follow-up. CSF GAP-43 concentration was significantly lower in progressive MS compared with HCs (p = 0.004) and RRMS (p =  < 0.001) and correlated negatively with disability (p = 0.026). However, DMTs did not alter CSF GAP-43. Interestingly, in RRMS CSF GAP-43 levels were higher in patients with signs of active inflammatory disease than in patients in remission (p = 0.042). According to CSF GAP-43 concentrations, regeneration seems reduced in progressive MS, increased during disease activity in RRMS but is unaffected by treatment of highly active DMTs.

Uric acid: a potential biomarker of multiple sclerosis and of its disability

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Marcello Moccia ◽  
Roberta Lanzillo ◽  
Raffaele Palladino ◽  
Cinzia Russo ◽  
Antonio Carotenuto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Longitudinal Design ◽  
Therapeutic Strategies ◽  
Healthy Controls ◽  
Nitrogen Species ◽  
Lower Serum ◽  
Secondary Progressive ◽  
Potential Biomarker ◽  
Relapsing Remitting

AbstractUric acid (UA) is a strong natural scavenger of reactive oxygen and nitrogen species, with evidence of possible use in the treatment of animal models of multiple sclerosis (MS). Consequently, serum UA has gained much attention as a possible biomarker of MS. We aim to investigate differences in serum UA levels between MS subjects and controls and evaluate possible relationships of UA with MS clinical features.We recruited relapsing-remitting and secondary progressive MS subjects and healthy controls and measured their serum UA levels. We excluded subjects presenting concomitant conditions affecting UA levels.MS subjects (n=362) and controls (n=181) were recruited by propensity score matching (PSM). Statistical analyses were corrected for age, gender, and renal function. MS subjects presented significantly lower serum UA levels than controls (analysis of variance, p=0.014, adjusted rOur findings support the importance of serum UA as a biomarker of MS disability and progression. Further studies with longitudinal design should be specifically designed to evaluate the importance of UA in the different stages of MS and in relation to distinct therapeutic strategies.

Spatiotemporal distribution of white matter lesions in relapsing–remitting and secondary progressive multiple sclerosis

2012 ◽  
Vol 18 (11) ◽  
pp. 1577-1584 ◽  
Author(s):  
Lukas Filli ◽  
Louis Hofstetter ◽  
Pascal Kuster ◽  
Stefan Traud ◽  
Nicole Mueller-Lenke ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Spatiotemporal Distribution ◽  
Centrum Semiovale ◽  
Cross Sectional ◽  
Secondary Progressive ◽  
Lateral Ventricles ◽  
Relapsing Remitting ◽  
T1 And T2

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS lesions show a typical distribution pattern and primarily affect the white matter (WM) in the periventricular zone and in the centrum semiovale. Objective: To track lesion development during disease progression, we compared the spatiotemporal distribution patterns of lesions in relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS). Methods: We used T1 and T2 weighted MR images of 209 RRMS and 62 SPMS patients acquired on two different 1.5 Tesla MR scanners in two clinical centers followed up for 25 (± 1.7) months. Both cross-sectional and longitudinal differences in lesion distribution between RRMS and SPMS patients were analyzed with lesion probability maps (LPMs) and permutation-based inference. Results: MS lesions clustered around the lateral ventricles and in the centrum semiovale. Cross-sectionally, compared to RRMS patients, the SPMS patients showed a significantly higher regional probability of T1 hypointense lesions ( p≤0.03) in the callosal body, the corticospinal tract, and other tracts adjacent to the lateral ventricles, but not of T2 lesions (peak probabilities were RRMS: T1 9%, T2 18%; SPMS: T1 21%, T2 27%). No longitudinal changes of regional T1 and T2 lesion volumes between baseline and follow-up scan were found. Conclusion: The results suggest a particular vulnerability to neurodegeneration during disease progression in a number of WM tracts.

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cytokine Production ◽  
Clinical Signs ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

scholarly journals Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Isobel A. Scarisbrick ◽  
Rachel Linbo ◽  
Alexander G. Vandell ◽  
Mark Keegan ◽  
Sachiko I. Blaber ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Neurons ◽  
Serine Proteases ◽  
Serum Levels ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Neurite Retraction ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Potential Activity

Abstract Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

scholarly journals Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis

2018 ◽  
Vol 76 (9) ◽  
pp. 588-591 ◽  
Author(s):  
Luciana Prats Branco ◽  
Tarso Adoni ◽  
Samira Luisa Apostolos-Pereira ◽  
Joseph Bruno Bidin Brooks ◽  
Eber Castro Correa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immunosorbent Assay ◽  
Treatment Options ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Antibodies ◽  
John Cunningham Virus ◽  
Blood Tests ◽  
Serological Profile

ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

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