Oligoclonal IgGs against DNA, Histones, and Myelin Basic Protein in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kostrikina IA ◽  
◽  
Granieri E ◽  
Nevinsky GA ◽  
◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Main Role ◽  
Barr Virus ◽  
The Central Nervous System ◽  
Epstein Barr ◽  
Ms Pathogenesis ◽  
Myelin Proteolipid

Multiple Sclerosis (MS) is known as a chronic demyelinating pathology of the central nervous system. The most accepted MS pathogenesis theory assigns the main role to demyelination of myelin-proteolipid shells due to inflammationrelated with autoimmune reactions. One of the features of MS patients is the enhanced synthesis of oligoclonal IgGs in the bone marrow Cerebrospinal Fluid (CSF). By antigen-specific immunoblotting after isoelectrofocusing of IgGs, oligoclonal IgGs in CSF of MS patients were revealed only against the components of Epstein-Barr virus and Chlamydia. However, there was still unknown to which human auto-antigens in MS patients oligoclonal IgGs may be produced. Here it was first shown that in the CSF of a narrow percentage of MS patients, oligoclonal IgGs are produced against their own antigens: DNA (24% patients), histones (20%), and myelin basic protein (12%). At the same time, the CSF of MS patients contains a very large amount of auto-IgGs-abzymes that hydrolyze DNA, histones, and myelin basic protein, which during isofocusing, are distributed throughout the gel from pH 3 to 10. It is concluded that these multiple IgGs-abzymes, which are dangerous to humans since stimulate development of MS, in the main are non-oligoclonal antibodies.

scholarly journals Extreme Diversity of IgGs Against Histones, DNA, and Myelin Basic Protein in the Cerebrospinal Fluid and Blood of Patients with Multiple Sclerosis

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 630 ◽  
Author(s):  
Irina A. Kostrikina ◽  
Valentina N. Buneva ◽  
Enrico Granieri ◽  
Georgy A. Nevinsky
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Relative Concentration ◽  
Correlation Coefficients ◽  
Hydrolysis Of ◽  
Hydrolysis Of Dna

It was recently shown that IgGs from sera of multiple sclerosis (MS) patients are active in the hydrolysis of DNA and myelin basic protein (MBP). We first analyzed the relative concentration of antibodies against five histones (H1, H2a, H2b, H3, and H4) in the cerebrospinal fluid (CSF) and serum of patients with MS. The relative concentrations of blood and CSF IgGs against histones and their activity in the hydrolysis of five histones varied greatly from patient to patient. However, all 28 IgG preparations were hydrolyzed from one to five histones. Relative activities and correlation coefficients among the activities of IgGs from serum and CSF in the hydrolysis of five histones (H1, H2a, H2b, H3, and H4), DNA, and MBP were calculated. It was shown that auto-IgGs from CSF and sera of MS patients are extremely heterogeneous in their affinity to histones, MBP, and DNA. The heterogeneity of IgG-abzymes hydrolyzing DNA, MBP, and histones from CSF and sera was also demonstrated using their isoelectrofocusing. The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10.

scholarly journals Epitope Analysis of Cerebrospinal Fluid IgG in Japanese Multiple Sclerosis Patients Using Phage Display Method

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Juichi Fujimori ◽  
Ichiro Nakashima ◽  
Kazuo Fujihara ◽  
Tatsuro Misu ◽  
Shigeru Sato ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Phage Display ◽  
Amino Acid Sequences ◽  
Barr Virus ◽  
Common Motif ◽  
Bystander Response ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Multiple Sclerosis Patients

To investigate the antigen recognized by cerebrospinal fluid (CSF) high affinity IgG in patients with multiple sclerosis (MS), the phage display method was applied to the CSF from 15 MS and 10 control patients. Peptide sequences recognized by MS and control CSF IgG were individual specific, and no common motif was found. Peptide sequences frequently showed homology to various kinds of amino acid sequences of ubiquitous viruses such as epstein barr virus (EBV) and herpes simplex virus (HSV), although the frequency was not specific to MS patients. MS CSF IgG may recognize various types of ubiquitous viral antigen and may be increased by a bystander response.

Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Epstein Barr Virus ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiple Sclerosis Patients

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

scholarly journals The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

2019 ◽  
Vol 20 (2) ◽  
pp. 303 ◽  
Author(s):  
Rachael Tarlinton ◽  
Timur Khaibullin ◽  
Evgenii Granatov ◽  
Ekaterina Martynova ◽  
Albert Rizvanov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Large Scale ◽  
Motor Impairment ◽  
Endogenous Retrovirus ◽  
Barr Virus ◽  
Scale Population ◽  
Epidemiological Risk ◽  
The Central Nervous System ◽  
Epstein Barr

Multiple sclerosis (MS) is a chronic debilitating inflammatory disease of unknown ethology targeting the central nervous system (CNS). MS has a polysymptomatic onset and is usually first diagnosed between the ages of 20–40 years. The pathology of the disease is characterized by immune mediated demyelination in the CNS. Although there is no clinical finding unique to MS, characteristic symptoms include sensory symptoms visual and motor impairment. No definitive trigger for the development of MS has been identified but large-scale population studies have described several epidemiological risk factors for the disease. This list is a confusing one including latitude, vitamin D (vitD) levels, genetics, infection with Epstein Barr Virus (EBV) and endogenous retrovirus (ERV) reactivation. This review will look at the evidence for each of these and the potential links between these disparate risk factors and the known molecular disease pathogenesis to describe potential hypotheses for the triggering of MS pathology.

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