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

• Main Authors: An Hotterbeekx, Melissa Krizia Vieri, Melanie Ramberger, Ashraf Jozefzoon-Aghai, Michel Mandro, Floribert Tepage, Alfred Dusabimana, Samir Kumar-Singh, Maarten J. Titulaer, Robert Colebunders
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Pathogens
• Subjects: onchocerciasis-associated epilepsy; nodding syndrome; leiomodin-1; autoimmune
• Online Access: https://www.mdpi.com/2076-0817/10/7/845

Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with <i>Onchocerca volvulus</i>. 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%) (<i>p =</i> 0.113) and 23/54 (43%) <i>(p =</i> 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between <i>O. volvulus</i> 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 <i>O. volvulus</i> infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.