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Immunization with neuronal antigens such as neurofilament light (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L), a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, although antibodies to <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L contribute to neurodegeneration and neurological disease. To address this, we examined the pathogenic role of antibodies directed to <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L <jats:italic>in\u00a0vitro<\/jats:italic> using spinal cord co\u2010cultures and <jats:italic>in\u00a0vivo<\/jats:italic> in experimental autoimmune encephalomyelitis (<jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content>) and optic neuritis animal models of multiple sclerosis. Here we show that peripheral injections of antibodies to <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L augmented clinical signs of neurological disease in acute <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content>, increased retinal ganglion cell loss in experimental optic neuritis and induced neurological signs following intracerebral injection into control mice. The pathogenicity of antibodies to <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L was also observed in spinal cord co\u2010cultures where axonal loss was induced. Taken together, our results reveal that as well as acting as reliable biomarkers of neuronal damage, antibodies to <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L exacerbate neurological disease, suggesting that antibodies to <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010L generated during disease may also be pathogenic and play a role in the progression of neurodegeneration.<\/jats:p>","DOI":"10.1111\/imm.12797","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T12:24:49Z","timestamp":1500380689000},"page":"580-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neurofilament light as an immune target for pathogenic 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Medicine RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Boon","sequence":"additional","affiliation":[{"name":"Bioceros Holdings BV Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Bosca","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK"},{"name":"MS Unit Neurology Department La Fe University Hospital Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Raffel","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London 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