Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy

2013 ◽  
Vol 19 (9) ◽  
pp. 1230-1233 ◽  
Author(s):  
Akiko Yokoseki ◽  
Etsuji Saji ◽  
Musashi Arakawa ◽  
Mariko Hokari ◽  
Takanobu Ishiguro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Ccr7 Expression ◽  
Blood Lymphocytes ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
Secondary Lymphoid Organs

Fingolimod acts as a functional antagonist of the sphingosine-1-phosphate receptor, and it traps lymphocytes in secondary lymphoid organs and precludes their migration into the central nervous system. We report the case of a patient who suffered a relatively severe relapse of multiple sclerosis (MS) during the initial 3 months of fingolimod therapy, with retention of CCR7 expression on CD4+ T cells in the cerebrospinal fluid (CSF) despite decreased numbers of lymphocytes and decreased expression of CCR7 on CD4+ T cells in the blood. These data suggest that fingolimod may cause differential effects on the CSF and blood lymphocytes of patients with MS during the initial months of therapy.

CHAPTER 9: Immunology of TBEV-Infections

2020 ◽  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Sample Collection ◽  
Tick Borne Encephalitis ◽  
Viral Infectious Disease ◽  
The Central Nervous System

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

Chapter 9: Immunology of TBEV-Infection

2021 ◽  
Author(s):  
Sara Gredmark-Russ ◽  
Renata Varnaite
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Sample Collection ◽  
Tick Borne Encephalitis ◽  
Viral Infectious Disease ◽  
The Central Nervous System

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

scholarly journals TGF-β in Mice Ameliorates Experimental Autoimmune Encephalomyelitis in Regulating NK Cell Activity

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1155-1160 ◽  
Author(s):  
J. Xu ◽  
Y. Wang ◽  
H. Jiang ◽  
M. Sun ◽  
J. Gao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Nk Cells ◽  
Nk Cell ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

Multiple sclerosis is a disease characterized by inflammation and demyelination located in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for multiple sclerosis (MS). Although the roles of T cells in MS/EAE have been well investigated, little is known about the functions of other immune cells in the neuroinflammation model. Here we found that an essential cytokine transforming growth factor β (TGF-β) which could mediate the differentiation of Th17/regulatory T cells was implicated in the natural killer (NK) cells’ activity in EAE. In EAE mice, TGF-β expression was first increased at the onset and then decreased at the peak, but the expressions of TGF-β receptors and downstream molecules were not affected in EAE. When we immunized the mice with MOG antigen, it was revealed that TGF-β treatment reduced susceptibility to EAE with a lower clinical score than the control mice without TGF-β. Consistently, inflammatory cytokine production was reduced in the TGF-β treated group, especially with downregulated pathogenic interleukin-17 in the central nervous system tissue. Furthermore, TGF-β could increase the transcription level of NK cell marker NCR1 both in the spleen and in the CNS without changing other T cell markers. Meanwhile TGF-β promoted the proliferation of NK cell proliferation. Taken together, our data demonstrated that TGF-β could confer protection against EAE model in mice through NK cells, which would be useful for the clinical therapy of MS.

Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients

2011 ◽  
Vol 18 (7) ◽  
pp. 1038-1041 ◽  
Author(s):  
Felipe von Glehn ◽  
Alessandro S Farias ◽  
Augusto C Penalva de Oliveira ◽  
Alfredo Damasceno ◽  
Ana Leda F Longhini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Oligoclonal Bands ◽  
Natalizumab Treatment ◽  
The Central Nervous System ◽  
Immunologic Abnormality ◽  
Csf Oligoclonal Bands ◽  
Multiple Sclerosis Patients

Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known.

scholarly journals Chemokines and Chemokine Receptors in Multiple Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Wenjing Cheng ◽  
Guangjie Chen
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Autoimmune Disease ◽  
Chemokine Receptors ◽  
Cell Subset ◽  
Small Peptide

Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.

FTY720 on the way from the base camp to the summit of the mountain: relevance for remyelination

2012 ◽  
Vol 18 (3) ◽  
pp. 258-263 ◽  
Author(s):  
M Kipp ◽  
S Amor
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Oral Disease ◽  
S1p Receptors ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

FTY720 (fingolimod; Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator, is the first oral disease-modifying therapy to be approved for the treatment of relapsing–remitting multiple sclerosis. FTY720 is rapidly converted in vivo to the active S-fingolimod-phosphate, which binds to S1P receptors. This action inhibits egress of lymphocytes from the lymph nodes, preventing entry into the blood and thus infiltration into the central nervous system. More recent studies, however, convincingly show that FTY720 crosses the blood–brain barrier, where it is thought to act on S1P receptors on cells within the central nervous system, such as astrocytes, oligodendrocytes or microglia. Here we discuss the evidence showing that FTY720 also plays a role in remyelination and repair within the brain. While the mechanisms of action still require firm elucidation, it is clear that FTY720 could also be reparative, extending its therapeutic potential for multiple sclerosis.

scholarly journals Blood and CSF Biomarker Dynamics in Multiple Sclerosis: Implications for Data Interpretation

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
M. J. Eikelenboom ◽  
B. M. J. Uitdehaag ◽  
A. Petzold
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Serum Levels ◽  
Disability Progression ◽  
Protein Biomarker ◽  
The Central Nervous System ◽  
Neuroaxonal Degeneration

Background. Disability in multiple sclerosis (MS) is related to neuroaxonal degeneration. A reliable blood biomarker for neuroaxonal degeneration is needed.Objectives. To explore the relationship between cerebrospinal fluid (CSF) and serum concentrations of a protein biomarker for neuroaxonal degeneration, the neurofilaments heavy chain (NfH).Methods. An exploratory cross-sectional (n=51) and longitudinal (n=34) study on cerebrospinal fluid (CSF) and serum NfH phosphoform levels in patients with MS. The expanded disability status scale (EDSS), CSF, and serum levels of NfH-SMI34 and NfH-SMI35 were quantified at baseline. Disability progression was assessed at 3-year followup.Results. At baseline, patients with primary progressive MS (PPMS, EDSS 6) and secondary progressive MS (SPMS, EDSS 6) were more disabled compared to patients with relapsing remitting MS (RRMS, EDSS 2,P<.0001). Serum and CSF NfH phosphoform levels were not correlated. Baseline serum levels of the NfH-SMI34 were significantly (P<.05) higher in patients with PPMS (2.05 ng/mL) compared to SPMS (0.03 ng/mL) and RRMS (1.56 ng/mL). In SPMS higher serum than CSF NfH-SMI34 levels predicted disability progression from baseline (ΔEDSS2,P<.05). In RRMS higher CSF than serum NfH-SMI35 levels predicted disability progression (ΔEDSS2,P<.05).Conclusion. Serum and CSF NfH-SMI34 and NfH-SMI35 levels did not correlate with each other in MS. The quantitative relationship of CSF and serum NfH levels suggests that neuroaxonal degeneration of the central nervous system is the likely cause for disability progression in RRMS. In more severely disabled patients with PP/SPMS, subtle pathology of the peripheral nervous system cannot be excluded as an alternative source for blood NfH levels. Therefore, the interpretation of blood protein biomarker data in diseases of the central nervous system (CNS) should consider the possibility that pathology of the peripheral nervous system (PNS) may influence the results.

Multiple Sclerosis: Monitoring Disease Activity and Progression

2017 ◽  
Author(s):  
Pavan Bhargava ◽  
Shiv Saidha
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Disease Activity ◽  
Cerebrospinal Fluid Biomarkers ◽  
The Central Nervous System ◽  
Degenerative Disorder ◽  
Clinical Measures ◽  
Assessment Strategies

Multiple sclerosis is a chronic inflammatory and degenerative disorder of the central nervous system. Measuring disease activity and progression are an integral part of the management of the disorder. A number of different approaches, including clinical measures, imaging metrics, and blood/cerebrospinal fluid biomarkers have been investigated for their utility in monitoring disease activity and progression. Each of these different approaches has certain advantages, as well as limitations, and this chapter provides an overview of these different assessment strategies.

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