Neurofilament light as an immune target for pathogenic antibodies

Puentes, F. et al. (2017) Neurofilament light as an immune target for pathogenic antibodies. Immunology, 152(4), pp. 580-588. (doi: 10.1111/imm.12797) (PMID:28718500)

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Abstract

Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunisation with neuronal antigens such as neurofilament light NF-L, a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, while antibodies to NF-L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF-L contribute to neurodegeneration and neurological disease. To address this, we examined the pathogenic role of antibodies directed to NF-L in vitro using spinal cord co-cultures and in vivo in experimental autoimmune encephalomyelitis (EAE) and optic neuritis animal models of multiple sclerosis. Here we show that peripheral injections of antibodies to NF-L augmented clinical signs of neurological disease in acute EAE, increased retinal ganglion cell loss in experimental optic neuritis and induced neurological signs following intracerebral injection into control mice. The pathogenicity of antibodies to NF-L was also observed in spinal cord co-cultures where axonal loss was induced. Taken together, our results reveal that as well as acting as reliable biomarkers of neuronal damage, antibodies to NF-L exacerbate neurological disease, suggesting that antibodies to NF-L generated during disease may also be pathogenic and play a role in the progression of neurodegeneration.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barnett, Professor Susan
Authors: Puentes, F., van der Star, B. J., Boomkamp, S. D., Kipp, M., Boon, L., Bosca, I., Raffel, J., Gnanapavan, S., van der Valk, P., Stephenson, J., Barnett, S. C., Baker, D., and Amor, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:Wiley
ISSN:0019-2805
ISSN (Online):1365-2567
Published Online:17 July 2017
Copyright Holders:Copyright © 2017 John Wiley & Sons Ltd
First Published:First published in Immunology 152(4):580-588
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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