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

Authors :
David W. Nauen
Michael C. Haffner
Juyun Kim
Qizhi Zheng
Hao Yin
Angelo M. DeMarzo
Vasiliki Mahairaki
Carlo Colantuoni
J. Geoffrey Pickering
Tory P. Johnson
Source :
Pathogens, Vol 9, Iss 12, p 1036 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

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.

Details

Language :
English
ISSN :
20760817
Volume :
9
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Pathogens
Publication Type :
Academic Journal
Accession number :
edsdoj.0e40889bd52430fa2f88c6044ef54b7
Document Type :
article
Full Text :
https://doi.org/10.3390/pathogens9121036