Overexpression of the ubiquitin‐editing enzyme A20 in the brain lesions of Multiple Sclerosis patients: moving from systemic to central nervous system inflammation

Multiple sclerosis is chronic inflammatory disease of the central nervous system in the development of which chemokines of the type Tx1 play the leading role. Chemokines and their receptors participate in the development of multiple sclerosis as a result of drawing immune cells into central nervous system. Mutation of CCR5 delta32 decreases functional activity of the appropriate receptor on cellular surface and thus can reduce migration of leucocytes into foci of injury. Aimed at studying the role of mutation in multiple sclerosis, we compared frequency of gene type CCR5 in peripheral mononuclears of 102 multiple sclerosis patients and in 136 healthy subjects. The results obtained allow to conclude that polymorphism of chemokine receptor gene CCR5del32 is not a leading factor in the susceptibility to multiple sclerosis in the studied population.

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HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population

Multiple Sclerosis Journal ◽

10.1177/1352458510376177 ◽

2010 ◽

Vol 16 (10) ◽

pp. 1173-1177 ◽

Cited By ~ 10

Author(s):

M. Shahbazi ◽

H. Ebadi ◽

D. Fathi ◽

D. Roshandel ◽

M. Mohamadhosseni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Promoter Polymorphism ◽

Exact Test ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Pcr Method ◽

Multiple Sclerosis Patients ◽

The Impact

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.

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Immune and central nervous system-related miRNAs expression profiling in monocytes of multiple sclerosis patients

Scientific Reports ◽

10.1038/s41598-020-63282-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Antonella Amoruso ◽

Maria Blonda ◽

Maira Gironi ◽

Roberta Grasso ◽

Valeria Di Francescantonio ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Expression Profiling ◽

Mirnas Expression ◽

Multiple Sclerosis Patients

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Naturally Presented Peptides on Major Histocompatibility Complex I and II Molecules Eluted from Central Nervous System of Multiple Sclerosis Patients

Molecular & Cellular Proteomics ◽

10.1074/mcp.m900001-mcp200 ◽

2009 ◽

Vol 8 (9) ◽

pp. 2090-2101 ◽

Cited By ~ 46

Author(s):

Nicolas Fissolo ◽

Sabrina Haag ◽

Katrien L. de Graaf ◽

Oliver Drews ◽

Stefan Stevanovic ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Major Histocompatibility Complex ◽

Complex I ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Multiple Sclerosis Patients ◽

Major Histocompatibility Complex I

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

Multiple Sclerosis Journal ◽

10.1177/1352458511428465 ◽

2011 ◽

Vol 18 (7) ◽

pp. 1038-1041 ◽

Cited By ~ 35

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.

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Inflammatory Demyelinating Central Nervous System Diseases in Childhood: Clinical and Paraclinical Profiles in 133 Patients

Autoimmune Diseases ◽

10.1155/2012/957802 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6

Author(s):

Derya Kaya ◽

Egemen İdiman ◽

Serkan Özakbaş

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Disease Onset ◽

Progressive Multiple Sclerosis ◽

Western Turkey ◽

Mri Features ◽

Cranial Mri ◽

Multiple Sclerosis Patients ◽

Demyelinating Disorders

In a retrospective review of patients with acquired demyelinating disorders of the central nervous system, 133 patients (5.6%) whose diseases started in childhood, were selected from 2369 patients, who had medical records in the Neurology Department of Dokuz Eylul University. Out of 133, 98 had relapsing remitting multiple sclerosis, 21 had secondary progressive multiple sclerosis, 8 had clinically isolated syndrome, 3 had neuromyelitis optica, 2 had Marburg disease, and 1 had radiologically isolated syndrome. In 55 patients (41.3%), disease onset was before age 16. Polysymptomatic presentation (22.6%) was the most common initial feature. The EDSS scores ranged from 0 to 9 with a median of 2.0 () for 126 patients. MRI records of 111 patients were obtained. 97 patients had clinically definite multiple sclerosis. 11 MS patients (11.3%) did not initially present the diagnostic MRI features. All of the remaining multiple sclerosis patients fulfilled Barkhof-Tintore criteria (100%) and 88.7% fulfilled KIDMUS criteria. Cranial MRI of NMO patients was normal. Our findings demonstrate some important clinical and paraclinical features that can help the literature on acquired demyelinating disorders of childhood by utilizing data from Western Turkey.

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Aino Virus Antigen in Brain Lesions of a Naturally Aborted Bovine Fetus

Veterinary Pathology ◽

10.1177/030098589803500511 ◽

1998 ◽

Vol 35 (5) ◽

pp. 409-411 ◽

Cited By ~ 15

Author(s):

Y. Noda ◽

Y. Uchinuno ◽

H. Shirakawa ◽

S. Nagasue ◽

N. Nagano ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Brain Lesion ◽

Neutralizing Antibody ◽

Virus Antigen ◽

Brain Lesions ◽

Significant Feature ◽

The Central Nervous System ◽

The Brain

A bovine fetus aborted at 187 days of gestation was serologically and immunohistopathologically examined. Serum and cerebrospinal fluid samples had high titers of virus-neutralizing antibody for Aino virus. A severe necrotizing encephalopathy was noted. Aino virus antigen was demonstrated in neuroglial cells within the brain lesion. The destruction of developing neuronal cells appeared to be a significant feature of the pathogenesis of lesions due to Aino virus infection in the central nervous system.

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Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

Clinical and Developmental Immunology ◽

10.1155/2013/708659 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 86

Author(s):

Genaro G. Ortiz ◽

Fermín P. Pacheco-Moisés ◽

Oscar K. Bitzer-Quintero ◽

Ana C. Ramírez-Anguiano ◽

Luis J. Flores-Alvarado ◽

...

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Tissue Injury ◽

Autoimmune Disorder ◽

Demyelinating Lesions ◽

The Central Nervous System ◽

The Brain ◽

And Oxidative Stress

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

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