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.

Highlights

  • Epitope from Epstein-Barr virus (EBV) lytic protein (BOLF1305–320) and two homologous peptides belonging to MAP_4027 protein (MAP_402718–32) and Human Interferon Regulatory Factor 5, interferon regulatory factor 5 (IRF5) protein (IRF5424–434)[3]

  • It has been shown that the Cerebral Spinal Fluid (CSF) from MS patients contains oligoclonal immunoglobulins (IgG), which are synthesized within the central nervous system and presumably related to the immune dysfunction, a characteristic feature of MS

  • The aim of this study was to investigate the presence of a specific humoral response mounted against peptides derived from EBV and Mycobacterium avium subsp. paratuberculosis (MAP) antigens homologues to host proteins in serum and in CSF of MS compared to Inflammatory and No inflammatory neurological disease

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Summary

Introduction

Epitope from EBV lytic protein (BOLF1305–320) and two homologous peptides belonging to MAP_4027 protein (MAP_402718–32) and Human Interferon Regulatory Factor 5, IRF5 protein (IRF5424–434)[3]. In this work we wanted to explore if we could find the same humoral response in CSF and serum against EBV epitopes deriving from EBV lytic and latent proteins, MAP and human homologous proteins in MS patients and in other neurological disease controls. Molecular mimicry between immunodominant epitopes deriving from bacterial and viral persistent antigens may be a decisive factor in directing autoimmunity to self-antigens in MS patients. For this reason it was important to explore if the epitopes from EBV and the other homologous MAP antigens were able to induce a humoral reactivity both in CSF and sera. The results could contribute to the understanding of chronic brain inflammation that contribute to MS pathogenesis

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