Epstein Barr Virus and Mycobacterium avium subsp. paratuberculosis peptides are recognized in sera and cerebrospinal fluid of MS patients

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Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) epitopes elicit a consistent humoral response in serum of multiple sclerosis patients, but the cross reactivity against the homologous myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5) has not been searched within the Cerebral Spinal Fluid (CSF). We evaluated in sera and CSF of patients with MS and with other neurological diseases (OND) the humoral response against EBV/MAP peptides and the IRF5/MBP. Our data showed that EBV and MAP peptides are able to induce a specific humoral immune response in MS patients compared to OND controls both in serum and in CSF. An intrathecal specific synthesis of IgG against MBP and their EBV and MAP homologous as indicated by the antibody index was observed in MS patients. The humoral response against EBV, MAP, MBP and IRF5 was significantly higher in MS patients compared to OND both in serum and in CSF. The higher presence of antibodies against MBP and their MAP and EBV homologous in CSF during relapses suggests a possible role of the pathogens in enhancing inflammation.

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Environmental risk factors for multiple sclerosis. Part I: the role of infection.

Alberto Ascherio, Kassandra L Munger (2007)

Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographic variations in MS frequency and the changes in risk that occur with migration. Epidemiological data provide some support for the "hygiene hypothesis," but with the additional proviso for a key role of Epstein-Barr virus (EBV) in determining MS risk. We show that whereas EBV stands out as the only infectious agent that can explain many of the key features of MS epidemiology, by itself the link between EBV and MS cannot explain the decline in risk among migrants from high to low MS prevalence areas. This decline implies that either EBV strains in low-risk areas have less propensity to cause MS, or that other infectious or noninfectious factors modify the host response to EBV or otherwise contribute to determine MS risk. The role of infectious factors is discussed here; in a companion article, we will examine the possible role of noninfectious factors and provide evidence that high levels of vitamin D may have a protective role, particularly during adolescence. The primary purpose of these reviews is to identify clues to the causes of MS and to evaluate the possibility of primary prevention.

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Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases.

Johan H. C. Reiber (1998)

The state of the art in routine CSF analysis is reviewed with particular reference to multiple sclerosis regarding: (1) The physiology and pathophysiology of blood-CSF barrier function and dysfunction with the CSF flow rate as main modulator of blood- and brain-derived protein concentrations in CSF; (2) The neuroimmunological aspects regarding (a) patterns of disease-related immunoglobulin class response (IgG, IgA, IgM) in actual Reiber graphs with reference to specific parameters and optional tests, and (b) the oligoclonal, polyspecific antibody synthesis in brain; (3) Particular marker proteins in CSF and blood for differential diagnosis of neurological diseases; (4) Mathematical base for evaluations of CSF data with an example of a multiple sclerosis patient for calculation of intrathecal immunoglobulin and antibody synthesis as well as Antibody Index.

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Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

Leonardo Sechi, Coad Dow (2015)

The factitive role of Mycobacterium avium ss. paratuberculosis (MAP) in Crohn’s disease has been debated for more than a century. The controversy is due to the fact that Crohn’s disease is so similar to a disease of MAP-infected ruminant animals, Johne’s disease; and, though MAP can be readily detected in the infected ruminants, it is much more difficult to detect in humans. Molecular techniques that can detect MAP in pathologic Crohn’s specimens as well as dedicated specialty labs successful in culturing MAP from Crohn’s patients have provided strong argument for MAP’s role in Crohn’s disease. Perhaps more incriminating for MAP as a zoonotic agent is the increasing number of diseases with which MAP has been related: Blau syndrome, type 1 diabetes, Hashimoto thyroiditis, and multiple sclerosis. In this article, we debate about genetic susceptibility to mycobacterial infection and human exposure to MAP; moreover, it suggests that molecular mimicry between protein epitopes of MAP and human proteins is a likely bridge between infection and these autoimmune disorders.

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Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 09 March 2016

Publication date Collection: 2016

Volume: 6

Electronic Location Identifier: 22401

Affiliations

[1 ]Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari , Viale San Pietro 43b, 07100 Sassari, Italy

[2 ]Centro Sclerosi Multipla, Dipartimento di Sanità Pubblica Medicina Clinica e Molecolare, Università di Cagliari , Via Is Guadazzonis 2, 09126 Cagliari, Italy

[3 ]Dipartimento di Scienze Mediche “Mario Aresu”, Università di Cagliari , 09126 Cagliari, Italy

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[a ] sechila@ 123456uniss.it

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Publisher Item ID: srep22401

DOI: 10.1038/srep22401

PMC ID: 4783662

PubMed ID: 26956729

SO-VID: 747208b1-5d50-49fe-b952-ba132d939d30

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Epstein Barr Virus and Mycobacterium avium subsp. paratuberculosis peptides are recognized in sera and cerebrospinal fluid of MS patients

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IET: COVID-19 related research

Most cited references 18

Environmental risk factors for multiple sclerosis. Part I: the role of infection.

Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases.

Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

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