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Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides

IgG oligoclonal bands (OCBs) are present in the cerebrospinal fluid (CSF) of more than 95% of patients with multiple sclerosis (MS), and are considered to be the immunological hallmark of disease. However, the target specificities of the IgG in MS OCBs have remained undiscovered. Nevertheless, evide...

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Autores principales: Graner, Michael, Pointon, Tiffany, Manton, Sean, Green, Miyoko, Dennison, Kathryn, Davis, Mollie, Braiotta, Gino, Craft, Julia, Edwards, Taylor, Polonsky, Bailey, Fringuello, Anthony, Vollmer, Timothy, Yu, Xiaoli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034880/
https://www.ncbi.nlm.nih.gov/pubmed/32084151
http://dx.doi.org/10.1371/journal.pone.0228883
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author Graner, Michael
Pointon, Tiffany
Manton, Sean
Green, Miyoko
Dennison, Kathryn
Davis, Mollie
Braiotta, Gino
Craft, Julia
Edwards, Taylor
Polonsky, Bailey
Fringuello, Anthony
Vollmer, Timothy
Yu, Xiaoli
author_facet Graner, Michael
Pointon, Tiffany
Manton, Sean
Green, Miyoko
Dennison, Kathryn
Davis, Mollie
Braiotta, Gino
Craft, Julia
Edwards, Taylor
Polonsky, Bailey
Fringuello, Anthony
Vollmer, Timothy
Yu, Xiaoli
author_sort Graner, Michael
collection PubMed
description IgG oligoclonal bands (OCBs) are present in the cerebrospinal fluid (CSF) of more than 95% of patients with multiple sclerosis (MS), and are considered to be the immunological hallmark of disease. However, the target specificities of the IgG in MS OCBs have remained undiscovered. Nevertheless, evidence that OCBs are associated with increased levels of disease activity and disability support their probable pathological role in MS. We investigated the antigen specificity of individual MS CSF IgG from 20 OCB-positive patients and identified 40 unique peptides by panning phage-displayed random peptide libraries. Utilizing our unique techniques of phage-mediated real-time Immuno-PCR and phage-probed isoelectric focusing immunoblots, we demonstrated that these peptides were targeted by intrathecal oligoclonal IgG antibodies of IgG1 and IgG3 subclasses. In addition, we showed that these peptides represent epitopes sharing sequence homologies with proteins of viral origin, and proteins involved in cell stress, apoptosis, and inflammatory processes. Although homologous peptides were found within individual patients, no shared peptide sequences were found among any of the 42 MS and 13 inflammatory CSF control specimens. The distinct sets of oligoclonal IgG-reactive peptides identified by individual MS CSF suggest that the elevated intrathecal antibodies may target patient-specific antigens.
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spelling pubmed-70348802020-02-27 Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides Graner, Michael Pointon, Tiffany Manton, Sean Green, Miyoko Dennison, Kathryn Davis, Mollie Braiotta, Gino Craft, Julia Edwards, Taylor Polonsky, Bailey Fringuello, Anthony Vollmer, Timothy Yu, Xiaoli PLoS One Research Article IgG oligoclonal bands (OCBs) are present in the cerebrospinal fluid (CSF) of more than 95% of patients with multiple sclerosis (MS), and are considered to be the immunological hallmark of disease. However, the target specificities of the IgG in MS OCBs have remained undiscovered. Nevertheless, evidence that OCBs are associated with increased levels of disease activity and disability support their probable pathological role in MS. We investigated the antigen specificity of individual MS CSF IgG from 20 OCB-positive patients and identified 40 unique peptides by panning phage-displayed random peptide libraries. Utilizing our unique techniques of phage-mediated real-time Immuno-PCR and phage-probed isoelectric focusing immunoblots, we demonstrated that these peptides were targeted by intrathecal oligoclonal IgG antibodies of IgG1 and IgG3 subclasses. In addition, we showed that these peptides represent epitopes sharing sequence homologies with proteins of viral origin, and proteins involved in cell stress, apoptosis, and inflammatory processes. Although homologous peptides were found within individual patients, no shared peptide sequences were found among any of the 42 MS and 13 inflammatory CSF control specimens. The distinct sets of oligoclonal IgG-reactive peptides identified by individual MS CSF suggest that the elevated intrathecal antibodies may target patient-specific antigens. Public Library of Science 2020-02-21 /pmc/articles/PMC7034880/ /pubmed/32084151 http://dx.doi.org/10.1371/journal.pone.0228883 Text en © 2020 Graner et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Graner, Michael
Pointon, Tiffany
Manton, Sean
Green, Miyoko
Dennison, Kathryn
Davis, Mollie
Braiotta, Gino
Craft, Julia
Edwards, Taylor
Polonsky, Bailey
Fringuello, Anthony
Vollmer, Timothy
Yu, Xiaoli
Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides
title Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides
title_full Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides
title_fullStr Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides
title_full_unstemmed Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides
title_short Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides
title_sort oligoclonal igg antibodies in multiple sclerosis target patient-specific peptides
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034880/
https://www.ncbi.nlm.nih.gov/pubmed/32084151
http://dx.doi.org/10.1371/journal.pone.0228883
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