Cargando…

Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons

Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous syst...

Descripción completa

Detalles Bibliográficos
Autores principales: Nauen, David W., Haffner, Michael C., Kim, Juyun, Zheng, Qizhi, Yin, Hao, DeMarzo, Angelo M., Mahairaki, Vasiliki, Colantuoni, Carlo, Pickering, J. Geoffrey, Johnson, Tory P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763904/
https://www.ncbi.nlm.nih.gov/pubmed/33321732
http://dx.doi.org/10.3390/pathogens9121036
_version_ 1783628129203388416
author Nauen, David W.
Haffner, Michael C.
Kim, Juyun
Zheng, Qizhi
Yin, Hao
DeMarzo, Angelo M.
Mahairaki, Vasiliki
Colantuoni, Carlo
Pickering, J. Geoffrey
Johnson, Tory P.
author_facet Nauen, David W.
Haffner, Michael C.
Kim, Juyun
Zheng, Qizhi
Yin, Hao
DeMarzo, Angelo M.
Mahairaki, Vasiliki
Colantuoni, Carlo
Pickering, J. Geoffrey
Johnson, Tory P.
author_sort Nauen, David W.
collection PubMed
description Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous system (CNS) damage. However, as leiomodin-1 expression and epitope availability in human neurons remains uncharacterized, the relevance of leiomodin-1 autoimmunity is unknown. Leiomodin-1 transcript expression was assessed in silico using publicly available ribonucleic acid (RNA) sequencing databases and in tissue by in situ hybridization and quantitative polymerase chain reaction. Abundance and subcellular localization were examined by cell fractionation and immunoblotting. Leiomodin-1 transcripts were expressed in cells of the CNS, including neurons and astrocytes. Protein was detectable from all brain regions examined as well as from representative cell lines and in vitro differentiated neurons and astrocytes. Leiomodin-1 was expressed on the membrane of newly formed neurons, but not neural progenitor cells or mature neurons. Importantly, leiomodin-1 antibodies were only toxic to cells expressing leiomodin-1 on the membrane. Our findings provide evidence that leiomodin-1 is expressed in human neurons and glia. Furthermore, we show membrane expression mediates leiomodin-1 antibody toxicity, suggesting these antibodies may play a role in pathogenesis.
format Online
Article
Text
id pubmed-7763904
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77639042020-12-27 Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons Nauen, David W. Haffner, Michael C. Kim, Juyun Zheng, Qizhi Yin, Hao DeMarzo, Angelo M. Mahairaki, Vasiliki Colantuoni, Carlo Pickering, J. Geoffrey Johnson, Tory P. Pathogens Article Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous system (CNS) damage. However, as leiomodin-1 expression and epitope availability in human neurons remains uncharacterized, the relevance of leiomodin-1 autoimmunity is unknown. Leiomodin-1 transcript expression was assessed in silico using publicly available ribonucleic acid (RNA) sequencing databases and in tissue by in situ hybridization and quantitative polymerase chain reaction. Abundance and subcellular localization were examined by cell fractionation and immunoblotting. Leiomodin-1 transcripts were expressed in cells of the CNS, including neurons and astrocytes. Protein was detectable from all brain regions examined as well as from representative cell lines and in vitro differentiated neurons and astrocytes. Leiomodin-1 was expressed on the membrane of newly formed neurons, but not neural progenitor cells or mature neurons. Importantly, leiomodin-1 antibodies were only toxic to cells expressing leiomodin-1 on the membrane. Our findings provide evidence that leiomodin-1 is expressed in human neurons and glia. Furthermore, we show membrane expression mediates leiomodin-1 antibody toxicity, suggesting these antibodies may play a role in pathogenesis. MDPI 2020-12-10 /pmc/articles/PMC7763904/ /pubmed/33321732 http://dx.doi.org/10.3390/pathogens9121036 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nauen, David W.
Haffner, Michael C.
Kim, Juyun
Zheng, Qizhi
Yin, Hao
DeMarzo, Angelo M.
Mahairaki, Vasiliki
Colantuoni, Carlo
Pickering, J. Geoffrey
Johnson, Tory P.
Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
title Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
title_full Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
title_fullStr Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
title_full_unstemmed Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
title_short Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
title_sort putative autoantigen leiomodin-1 is expressed in the human brain and in the membrane fraction of newly formed neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763904/
https://www.ncbi.nlm.nih.gov/pubmed/33321732
http://dx.doi.org/10.3390/pathogens9121036
work_keys_str_mv AT nauendavidw putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT haffnermichaelc putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT kimjuyun putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT zhengqizhi putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT yinhao putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT demarzoangelom putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT mahairakivasiliki putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT colantuonicarlo putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT pickeringjgeoffrey putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons
AT johnsontoryp putativeautoantigenleiomodin1isexpressedinthehumanbrainandinthemembranefractionofnewlyformedneurons