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No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy

Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European control...

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Autores principales: Hotterbeekx, An, Vieri, Melissa Krizia, Ramberger, Melanie, Jozefzoon-Aghai, Ashraf, Mandro, Michel, Tepage, Floribert, Dusabimana, Alfred, Kumar-Singh, Samir, Titulaer, Maarten J., Colebunders, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308601/
https://www.ncbi.nlm.nih.gov/pubmed/34357995
http://dx.doi.org/10.3390/pathogens10070845
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author Hotterbeekx, An
Vieri, Melissa Krizia
Ramberger, Melanie
Jozefzoon-Aghai, Ashraf
Mandro, Michel
Tepage, Floribert
Dusabimana, Alfred
Kumar-Singh, Samir
Titulaer, Maarten J.
Colebunders, Robert
author_facet Hotterbeekx, An
Vieri, Melissa Krizia
Ramberger, Melanie
Jozefzoon-Aghai, Ashraf
Mandro, Michel
Tepage, Floribert
Dusabimana, Alfred
Kumar-Singh, Samir
Titulaer, Maarten J.
Colebunders, Robert
author_sort Hotterbeekx, An
collection PubMed
description Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.
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spelling pubmed-83086012021-07-25 No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy Hotterbeekx, An Vieri, Melissa Krizia Ramberger, Melanie Jozefzoon-Aghai, Ashraf Mandro, Michel Tepage, Floribert Dusabimana, Alfred Kumar-Singh, Samir Titulaer, Maarten J. Colebunders, Robert Pathogens Article Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies. MDPI 2021-07-05 /pmc/articles/PMC8308601/ /pubmed/34357995 http://dx.doi.org/10.3390/pathogens10070845 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hotterbeekx, An
Vieri, Melissa Krizia
Ramberger, Melanie
Jozefzoon-Aghai, Ashraf
Mandro, Michel
Tepage, Floribert
Dusabimana, Alfred
Kumar-Singh, Samir
Titulaer, Maarten J.
Colebunders, Robert
No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy
title No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy
title_full No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy
title_fullStr No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy
title_full_unstemmed No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy
title_short No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy
title_sort no evidence for the involvement of leiomodin-1 antibodies in the pathogenesis of onchocerciasis-associated epilepsy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308601/
https://www.ncbi.nlm.nih.gov/pubmed/34357995
http://dx.doi.org/10.3390/pathogens10070845
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