EBNA1 (EBV protein) reactive to OCBs

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frodo
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EBNA1 (EBV protein) reactive to OCBs

Post by frodo » Fri Sep 25, 2020 7:21 am

Antibodies from multiple sclerosis brain identified Epstein-Barr virus nuclear antigen 1 & 2 epitopes which are recognized by oligoclonal bands

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Using a phage peptide library, we screened IgG purified from a postmortem brain plaque-periplaque from an acute MS patient. These IgG bound to phage peptides representing epitopes from Epstein-Barr virus nuclear antigens 1 and 2 (EBNA1/2),

The EBNA1 epitope in particular was recognized by IgG from 46 MS patients while IgG from inflammatory control patients had significantly less binding. Further, OCBs of MS patients from both sera and CSF also recognized the phage-display EBNA1 epitope.

These data reaffirm the potential of EBV infection and response as a factor in MS etiology and disease progression.

Background

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), the etiology of which is poorly understood. The most common laboratory abnormality associated with MS is increased intrathecal IgG synthesis and the presence of oligoclonal bands (OCBs) in the brain and cerebrospinal fluid (CSF). However, the major antigenic targets of these antibody responses are unknown. The risk of MS is increased after infectious mononucleosis (IM) dueto EBV infection, and MS patients have higher serum titers of anti-EBV antibodies than controlpopulations.

Objectives

To identify disease-relevant epitopes of IgG antibodies in MS.

Methods

We screened phage-displayed random peptide libraries (12-mer) with total IgG antibodies purified from the brain of a patient with acute MS. We identified and characterized the phage peptides for binding specificity to intrathecal IgG from patients with MS and from controls by ELISA, phage-mediated Immuno-PCR, and isoelectric focusing.

Results

Two phage peptides were identified that share sequence homologies with EBV nuclear antigens 1 and 2 (EBNA1 and EBNA2), respectively. The specificity of the EBV epitopes found by panning with MS brain IgG was confirmed by ELISA and competitive inhibition assays. Using a highly sensitive phage-mediated immuno-PCR assay, we determined specific bindings of the two EBV epitopes to IgG from CSF from 46 MS and 5 inflammatory control (IC) patients. MS CSF IgG have significantly higher bindings to EBNA1 epitope than to EBNA2 epitope, whereas EBNA1 and EBNA2 did not significantly differ in binding to IC CSF IgG. Further, the EBNA1 epitope was recognized by OCBs from multiple MS CSF as shown in blotting assays with samples separated by isoelectric focusing.

Conclusions

The EBNA1 epitope is reactive to MS intrathecal antibodies corresponding to oligoclonal bands. This reinforces the potential role of EBV in the etiology of MS.

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