Characterization of Th17 cells in multiple sclerosis patients and healthy controls

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.

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A Biosensor-Based Characterization of the Affinity Maturation of the Immune Response Against Interferon-β and Correlations with Neutralizing Antibodies in Treated Multiple Sclerosis Patients

Journal of Interferon & Cytokine Research ◽

10.1089/jir.2008.0144 ◽

2008 ◽

Vol 28 (12) ◽

pp. 713-724 ◽

Cited By ~ 13

Author(s):

Ebrima Gibbs ◽

Joel Oger

Keyword(s):

Multiple Sclerosis ◽

Immune Response ◽

Neutralizing Antibodies ◽

Affinity Maturation ◽

Interferon Β ◽

Multiple Sclerosis Patients

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Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients

Acta Neuropathologica ◽

10.1007/s00401-017-1744-4 ◽

2017 ◽

Vol 134 (3) ◽

pp. 383-401 ◽

Cited By ~ 48

Author(s):

Gijsbert P. van Nierop ◽

Marvin M. van Luijn ◽

Samira S. Michels ◽

Marie-Jose Melief ◽

Malou Janssen ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

White Matter ◽

Functional Characterization ◽

White Matter Lesions ◽

Multiple Sclerosis Patients

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Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318815513 ◽

2018 ◽

Vol 4 (4) ◽

pp. 205521731881551 ◽

Cited By ~ 3

Author(s):

L De Meijer ◽

D Merlo ◽

O Skibina ◽

EJ Grobbee ◽

J Gale ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Change ◽

Progressive Multiple Sclerosis ◽

Healthy Controls ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Serial Addition ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

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Characterization of the Specificity of Anti‐Neuronal Antibodies in Sera of Multiple Sclerosis Patients

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.668.3 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Elisa Takalo ◽

Autumn Fox ◽

George H. DeVries ◽

Roger H. Kennett

Keyword(s):

Multiple Sclerosis ◽

Multiple Sclerosis Patients

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T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

Multiple Sclerosis Journal ◽

10.1177/135245859600100503 ◽

1996 ◽

Vol 1 (5) ◽

pp. 270-278 ◽

Cited By ~ 26

Author(s):

CM Pelfrey ◽

LR Tranquill ◽

AB Vogt ◽

HF McFarland

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Demyelinating Disease ◽

T Cell Responses ◽

Proteolipid Protein ◽

T Cell Response ◽

Healthy Controls ◽

Cell Responses ◽

Hla Binding ◽

Multiple Sclerosis Patients

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which autoimmune T lymphocytes reacting with myelin antigens are believed to play a pathogenic role. Since HLA binding is involved in the selection of T cell responses, we have examined PLP peptide binding to HLA DR2, an HLA allele frequently found in MS patients. Both PLP 40–60 and PLP 89–106 show significant, high affinity binding to HLA DR2. We then tested whether responses to PLP peptides 40–60 and 89–106 are elevated in multiple sclerosis patients compared to matched controls. We also analysed T cell responses to MBP 87–106, which is considered to be the immunodominant region of MBP in humans. Here we demonstrate heterogenous T cell responses to PLP 40–60, PLP 89–106 and MBP 87–106 in both MS patients and controls. The overall number of TCL and the HLA restriction of those TCL did not vary significantly in the two groups. PLP 40–60 specific cytolytic TCL were increased in MS patients, whereas healthy controls had increased percentages of cytolytic TCL responding to PLP 89–106 and MBP 87–106. Although the data presented here shows heterogenous responses in T cell numbers, differences in numbers and specificity of cytolytic cells could be involved in the pathogenesis of autoimmune demyelinating disease.

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