scholarly journals Innate Immune System and Multiple Sclerosis. Granulocyte Numbers Are Reduced in Patients Affected by Relapsing-Remitting Multiple Sclerosis during the Remission Phase

2020 ◽  
Vol 9 (5) ◽  
pp. 1468
Author(s):  
Zbyšek Pavelek ◽  
Francesco Angelucci ◽  
Ondřej Souček ◽  
Jan Krejsek ◽  
Lukáš Sobíšek ◽  
...  

Background: Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. The cause of MS is still unknown, and the role of innate immunity is still poorly understood. Objective: The goal of this study was to understand whether, compared to healthy controls, the elements of innate immunity are altered in the blood of MS patients in the remitting phase. Methods: A total of 77 naïve MS patients and 50 healthy controls were included in this cohort study. Peripheral blood samples were collected and analyzed. All the calculations were performed with the statistical system R (r-project.org). Results: The results showed that MS patients had significantly lower relative representations of granulocytes than healthy controls, while the relative representations of monocytes remained unchanged. CD64- and PD-L1-positive granulocytes exhibited a nonsignificant decreasing trend, while granulocytes with other membrane markers remained noticeably unchanged. Conclusion: The results of this study suggest that studies of the causes of MS and its treatment should also be focused on the elements of the innate immune response.

Author(s):  
Chao Liu ◽  
Guansan Wang ◽  
Hong Liu ◽  
Yue Li ◽  
Jin Li ◽  
...  

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune diseases of the central nervous system with complex pathogeneses. NMO was once considered to be a severe variant of MS. There has been more evidence that a non-synonymous exchange (rs763361/Gly307Ser) in the gene for CD226 is linked to several autoimmune diseases including multiple sclerosis (MS). However, no studies have investigated the role of rs763361 in the pathogenesis of NMO.Objectives:The goal of our study is to evaluate the role of CD226 Gly307Ser in neuromyelitis optica (NMO) in Southern Han Chinese.Methods:Eight-nine NMO patients, 93 relapsing-remitting multiple sclerosis (RRMS) patients, and 122 controls (CTLs) were enrolled. The rs763361 alleles of the subjects were determined by sequencing-based typing.Results:The results strongly support that the TT genotypes are associated with NMO but are not significantly correlated with susceptibility for MS.Conclusions:CD226 Gly307Ser may correlate with risk of NMO in Southern Han Chinese.


Author(s):  
Aneta R. Borkowska ◽  
Beata Daniluk ◽  
Katarzyna Adamczyk

Multiple sclerosis (MS) is a progressive chronic disease of the Central Nervous System (CNS). Cognitive decline occurs rather rarely in relapsing–remitting multiple sclerosis (RRMS) compared to other types. The present study aimed to assess executive functions (EF) in relation to clinical and demographic variables in patients with RRMS. The study involved 22 individuals with RRMS (aged 23 to 49 years) and 22 matching controls. All the individuals with RRMS were in the remission phase. The assessments were carried out using MoCA, BDI-II, Halstead Category Test, Porteus Maze Test, verbal fluency tasks and Stroop Colour-Word Interference Test. The findings show that the two groups differed significantly in all the tests. All patients with RRMS in the remission phase presented at least one cognitive deficit, observed in general cognitive functioning, abstract reasoning or other executive functions, i.e., fluency, interference suppression, planning, or ability to modify activity in response to feedback. The deficits in most cases (except for those measured with the MoCA, Category Tests and phonemic fluency), are not related to intensity of depression and duration of the disease. Findings suggest that the diagnostic process in the case of patients with RRMS may include psychological assessment focusing on potentially existing cognitive, mainly executive, deficits and their severity.


2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  

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.


2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  

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.


2020 ◽  
Vol 21 (23) ◽  
pp. 9249
Author(s):  
Lars Masanneck ◽  
Susann Eichler ◽  
Anna Vogelsang ◽  
Melanie Korsen ◽  
Heinz Wiendl ◽  
...  

Cyclic GMP-AMP-synthase is a sensor of endogenous nucleic acids, which subsequently elicits a stimulator of interferon genes (STING)-dependent type I interferon (IFN) response defending us against viruses and other intracellular pathogens. This pathway can drive pathological inflammation, as documented for type I interferonopathies. In contrast, specific STING activation and subsequent IFN-β release have shown beneficial effects on experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Although less severe cases of relapse-remitting MS (RRMS) are treated with IFN-β, there is little information correlating aberrant type I IFN signaling and the pathologic conditions of MS. We hypothesized that there is a link between STING activation and the endogenous production of IFN-β during neuroinflammation. Gene expression analysis in EAE mice showed that Sting level decreased in the peripheral lymphoid tissue, while its level increased within the central nervous system over the course of the disease. Similar patterns could be verified in peripheral immune cells during the acute phases of RRMS in comparison to remitting phases and appropriately matched healthy controls. Our study is the first to provide evidence that the STING/IFN-β-axis is downregulated in RRMS patients, meriting further intensified research to understand its role in the pathophysiology of MS and potential translational applications.


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