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

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