Neurofilament light as an immune target for pathogenic antibodies

Fabiola Puentes, Baukje J van der Star, Stephanie D Boomkamp, Markus Kipp, Louis Boon, Isabel Bosca, Joel Raffel, Sharmilee Gnanapavan, Paul van der Valk, Jodie Stephenson, Susan C Barnett, David Baker, Sandra Amor

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunization 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, although 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.

Original languageEnglish
Pages (from-to)580-588
Number of pages9
JournalImmunology
Volume152
Issue number4
DOIs
Publication statusPublished - Dec 2017

Cite this

Puentes, F., van der Star, B. J., Boomkamp, S. D., Kipp, M., Boon, L., Bosca, I., ... Amor, S. (2017). Neurofilament light as an immune target for pathogenic antibodies. Immunology, 152(4), 580-588. https://doi.org/10.1111/imm.12797