Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus

Tory P. Johnson, Richa Tyagi, Paul R. Lee, Myoung Hwa Lee, Kory R. Johnson, Jeffrey Kowalak, Abdel Elkahloun, Marie Medynets, Alina Hategan, Joseph Kubofcik, James Sejvar, Jeffrey Ratto, Sudhir Bunga, Issa Makumbi, Jane R. Aceng, Thomas B. Nutman, Scott F. Dowell, Avindra Nath

Research output: Contribution to journalArticle

Abstract

Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoanti-bodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.

Original languageEnglish (US)
Article numbereaaf6953
JournalScience Translational Medicine
Volume9
Issue number377
DOIs
StatePublished - Feb 15 2017

ASJC Scopus subject areas

  • Medicine(all)

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    Johnson, T. P., Tyagi, R., Lee, P. R., Lee, M. H., Johnson, K. R., Kowalak, J., Elkahloun, A., Medynets, M., Hategan, A., Kubofcik, J., Sejvar, J., Ratto, J., Bunga, S., Makumbi, I., Aceng, J. R., Nutman, T. B., Dowell, S. F., & Nath, A. (2017). Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus. Science Translational Medicine, 9(377), [eaaf6953]. https://doi.org/10.1126/scitranslmed.aaf6953