Epstein Barr Virus and Mycobacterium avium subsp. paratuberculosis peptides are recognized in sera and cerebrospinal
Giuseppe Mameli1, Eleonora Cocco2, Jessica Frau2
1Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Viale San Pietro 43b, 07100 Sassari, Italy.
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.
Insights
This study reveals that Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) trigger specific immune responses in multiple sclerosis (MS) patients. These responses, particularly in cerebrospinal fluid (CSF), suggest a role for these pathogens in MS inflammation.
Area of Science:
- Neuroimmunology
- Infectious Immunology
Background:
- Multiple Sclerosis (MS) involves immune responses against myelin.
- Cross-reactivity of immune responses to pathogens like Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) with myelin antigens is suspected but not fully explored in cerebrospinal fluid (CSF).
Purpose of the Study:
- To investigate the humoral immune response against MAP and EBV peptides and their homologous antigens, myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5), in the serum and CSF of MS patients.
- To determine if these responses are specific to MS and correlate with disease activity.
Main Methods:
- Analysis of serum and CSF samples from patients with MS and other neurological diseases (OND).
- Evaluation of humoral immune response (antibody levels and intrathecal synthesis) against EBV/MAP peptides and IRF5/MBP.
- Comparison of antibody levels between MS patients and OND controls.
Main Results:
- Epstein-Barr virus (EBV) and Mycobacterium avium subsp. paratuberculosis (MAP) peptides induced a specific humoral immune response in MS patients compared to OND controls in both serum and CSF.
- Intrathecal synthesis of IgG against myelin basic protein (MBP) and homologous EBV/MAP antigens was observed in MS patients.
- Antibody levels against EBV, MAP, MBP, and IRF5 were significantly higher in MS patients than in OND controls.
- Elevated antibodies against MBP and their MAP/EBV homologs in CSF during relapses suggest a role in enhancing inflammation.
Conclusions:
- The study demonstrates a specific humoral immune response to EBV and MAP in MS patients, with evidence of intrathecal synthesis against MBP and homologous antigens.
- These findings suggest a potential role for EBV and MAP in the pathogenesis and inflammation of multiple sclerosis, particularly during relapses.
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