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Sci Transl Med. 2017 Feb 15;9(377). pii: eaaf6953. doi: 10.1126/scitranslmed.aaf6953.

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

Author information

1
Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
2
Bioinformatics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
3
Clinical Proteomics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
4
Microarray Core Facility, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
5
Neural Differentiation Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
6
Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
7
Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
8
Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
9
Ministry of Health, Kampala, Uganda.
10
Bill & Melinda Gates Foundation, Seattle, WA 98109, USA.
11
Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. natha@ninds.nih.gov.

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.

PMID:
28202777
PMCID:
PMC5434766
DOI:
10.1126/scitranslmed.aaf6953
[Indexed for MEDLINE]
Free PMC Article

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