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Article

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

1
Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
2
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
3
Robarts Research Institute, Western University, London, ON N6A 3K7, Canada
4
Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
5
Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21287, USA
6
Department of Medicine, Western University, London, ON N6A 3K7, Canada
7
Department of Medical Biophysics, Western University, London, ON N6A 3K7, Canada
8
Department of Biochemistry, Western University, London, ON N6A 3K7, Canada
*
Author to whom correspondence should be addressed.
Pathogens 2020, 9(12), 1036; https://doi.org/10.3390/pathogens9121036
Received: 18 November 2020 / Revised: 7 December 2020 / Accepted: 8 December 2020 / Published: 10 December 2020
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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. View Full-Text
Keywords: nodding syndrome; leiomodin-1; autoantibody; CNS; neuron; membrane nodding syndrome; leiomodin-1; autoantibody; CNS; neuron; membrane
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MDPI and ACS Style

Nauen, D.W.; Haffner, M.C.; Kim, J.; Zheng, Q.; Yin, H.; DeMarzo, A.M.; Mahairaki, V.; Colantuoni, C.; Pickering, J.G.; Johnson, T.P. Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons. Pathogens 2020, 9, 1036. https://doi.org/10.3390/pathogens9121036

AMA Style

Nauen DW, Haffner MC, Kim J, Zheng Q, Yin H, DeMarzo AM, Mahairaki V, Colantuoni C, Pickering JG, Johnson TP. Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons. Pathogens. 2020; 9(12):1036. https://doi.org/10.3390/pathogens9121036

Chicago/Turabian Style

Nauen, David W.; Haffner, Michael C.; Kim, Juyun; Zheng, Qizhi; Yin, Hao; DeMarzo, Angelo M.; Mahairaki, Vasiliki; Colantuoni, Carlo; Pickering, J. G.; Johnson, Tory P. 2020. "Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons" Pathogens 9, no. 12: 1036. https://doi.org/10.3390/pathogens9121036

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