Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with . 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%) ( 0.113) and 23/54 (43%) 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between 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 infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.
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http://dx.doi.org/10.3390/pathogens10070845 | DOI Listing |
Lancet Glob Health
July 2024
Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Background: Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment.
Methods: In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda.
Biochem Biophys Rep
September 2023
Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada.
Nodding syndrome is a neurological disease of children in northern Uganda. Infection with the nematode parasite has been epidemiologically implicated as the cause of the disease. It has been proposed that an autoantibody directed against the human protein leiomodin-1 cross reacts with a tropomyosin-like nematode protein, thus suggesting that nodding syndrome is an autoimmune brain disease due to extra-cerebral parasitism.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
March 2023
From the Department of Neurology (R.M.), David Geffen School of Medicine at University of California Los Angeles; Kampala MRI Centre (S.K.L., M.K.), Uganda; Department of Radiological Sciences (N.S.), David Geffen School of Medicine, University of California Los Angeles, CA; Division of General Internal Medicine and Health Services Research (N.J.J.), David Geffen School of Medicine at UCLA; Centre of Tropical Neuroscience (P.R.A., R.A., R.I.), Kitgum Site, Uganda; Makerere University (R.A., R.J.O., R.I.), College of Health Sciences, Kampala, Uganda; Laboratory of Parasitic Diseases (J.K., T.N.), National Institutes of Health, Bethesda, MD; Centre for Tropical Medicine and Global Health (K.M., R.I.), Nuffield Department of Medicine, University of Oxford, United Kingdom; Department of Psychiatry (C.N.), University of Oxford, United Kingdom; and Nuffield Department of Clinical Neurosciences (A.V.), University of Oxford, United Kingdom.
Background And Objective: Nodding syndrome (NS) is a unique childhood-onset epileptic disorder that occurs predominantly in several regions of sub-Saharan Africa. The disease has been associated with -induced immune responses and possible cross-reactivity with host proteins. The aim of this study was to compare structural changes in the brain on MRI between NS and other forms of onchocerciasis-associated epilepsies (OAEs) and to relate structural changes to the Ov-induced immune responses and level of disability.
View Article and Find Full Text PDFPathogens
July 2021
Global Health Institute, University of Antwerp, 2610 Antwerp, Belgium.
Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with . 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).
View Article and Find Full Text PDFPathogens
December 2020
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Nodding syndrome is a pediatric epilepsy disorder associated with infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous system (CNS) damage. However, as leiomodin-1 expression and epitope availability in human neurons remains uncharacterized, the relevance of leiomodin-1 autoimmunity is unknown.
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