Cerebrospinal fluid CD4+T cells from a multiple sclerosis patient cross-recognize Epstein-Barr virus and myelin basic protein

2004 ◽  
Vol 10 (5) ◽  
pp. 278-283 ◽  
Author(s):  
Trygve Holmøy ◽  
Espen Østhagen Kvale ◽  
Frode Vartdal
Author(s):  
Kostrikina IA ◽  
◽  
Granieri E ◽  
Nevinsky GA ◽  
◽  
...  

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.


2010 ◽  
Vol 225 (1-2) ◽  
pp. 167-170 ◽  
Author(s):  
Emilie Jaquiéry ◽  
Samantha Jilek ◽  
Myriam Schluep ◽  
Géraldine Le Goff ◽  
Miguel Garcia ◽  
...  

Immunology ◽  
2017 ◽  
Vol 152 (4) ◽  
pp. 660-676 ◽  
Author(s):  
Maria T. Cencioni ◽  
Roberta Magliozzi ◽  
Richard Nicholas ◽  
Rehiana Ali ◽  
Omar Malik ◽  
...  

2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  

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.


Immunology ◽  
2013 ◽  
Vol 139 (4) ◽  
pp. 533-544 ◽  
Author(s):  
Sandra A. Calarota ◽  
Antonella Chiesa ◽  
Paola Zelini ◽  
Giuditta Comolli ◽  
Lorenzo Minoli ◽  
...  

2014 ◽  
Vol 20 (14) ◽  
pp. 1825-1832 ◽  
Author(s):  
Michael P Pender ◽  
Peter A Csurhes ◽  
Casey MM Pfluger ◽  
Scott R Burrows

Background: Patients with multiple sclerosis (MS) have a deficiency of circulating CD8+ T cells, which might impair control of Epstein–Barr virus (EBV) and predispose to MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. Based on the expression of CD45RA and CD62L, CD4+ T cells and CD8+ T cells can be subdivided into four subsets with distinct homing and functional properties, namely: naïve, central memory, effector memory (EM) and effector memory re-expressing CD45RA (EMRA) cells. Objective: Our aim was to determine which memory subsets are involved in the CD8+ T cell deficiency and how these relate to clinical course. Methods: We used flow cytometry to analyze the memory phenotypes of T cells in the blood of 118 MS patients and 112 healthy subjects. Results: MS patients had a decreased frequency of EM (CD45RA–CD62L–) and EMRA (CD45RA+CD62L–) CD8+ T cells, which was present at the onset of disease and persisted throughout the clinical course. The frequencies of CD4+ EM and EMRA T cells were normal. Conclusion: Deficiency of effector memory CD8+ T cells is an early and persistent feature of MS and might underlie the impaired CD8+ T cell control of EBV.


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