Cargando…

Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study

The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expressi...

Descripción completa

Detalles Bibliográficos
Autores principales: Kusner, Linda L., Ciesielski, Michael J., Marx, Alexander, Kaminski, Henry J., Fenstermaker, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106794/
https://www.ncbi.nlm.nih.gov/pubmed/25050620
http://dx.doi.org/10.1371/journal.pone.0102231
_version_ 1782327529634267136
author Kusner, Linda L.
Ciesielski, Michael J.
Marx, Alexander
Kaminski, Henry J.
Fenstermaker, Robert A.
author_facet Kusner, Linda L.
Ciesielski, Michael J.
Marx, Alexander
Kaminski, Henry J.
Fenstermaker, Robert A.
author_sort Kusner, Linda L.
collection PubMed
description The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.
format Online
Article
Text
id pubmed-4106794
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41067942014-07-23 Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study Kusner, Linda L. Ciesielski, Michael J. Marx, Alexander Kaminski, Henry J. Fenstermaker, Robert A. PLoS One Research Article The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders. Public Library of Science 2014-07-22 /pmc/articles/PMC4106794/ /pubmed/25050620 http://dx.doi.org/10.1371/journal.pone.0102231 Text en © 2014 Kusner 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kusner, Linda L.
Ciesielski, Michael J.
Marx, Alexander
Kaminski, Henry J.
Fenstermaker, Robert A.
Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study
title Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study
title_full Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study
title_fullStr Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study
title_full_unstemmed Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study
title_short Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study
title_sort survivin as a potential mediator to support autoreactive cell survival in myasthenia gravis: a human and animal model study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106794/
https://www.ncbi.nlm.nih.gov/pubmed/25050620
http://dx.doi.org/10.1371/journal.pone.0102231
work_keys_str_mv AT kusnerlindal survivinasapotentialmediatortosupportautoreactivecellsurvivalinmyastheniagravisahumanandanimalmodelstudy
AT ciesielskimichaelj survivinasapotentialmediatortosupportautoreactivecellsurvivalinmyastheniagravisahumanandanimalmodelstudy
AT marxalexander survivinasapotentialmediatortosupportautoreactivecellsurvivalinmyastheniagravisahumanandanimalmodelstudy
AT kaminskihenryj survivinasapotentialmediatortosupportautoreactivecellsurvivalinmyastheniagravisahumanandanimalmodelstudy
AT fenstermakerroberta survivinasapotentialmediatortosupportautoreactivecellsurvivalinmyastheniagravisahumanandanimalmodelstudy