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Linking parasitic infection to autoimmune epilepsy
Nodding syndrome is a unique seizure disorder affecting children in parts of East Africa. The cause of nodding syndrome has been an enigma, although an epidemiological association with the parasite Onchocerca volvulus has been established. Johnson et al. demonstrate that patients with nodding syndrome have autoantibodies to leiomodin-1 that are neurotoxic in vitro and that leiomodin-1 is expressed in regions of the brain affected during disease. Leiomodin-1 antibodies cross-react with O. volvulus proteins, linking the parasite to the autoantibody. Thus, nodding syndrome may be an autoimmune epilepsy initiated by a parasitic infection and may be preventable by treatment with antiparasitic strategies such as the drug ivermectin.
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 autoantibodies 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.
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