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November 2021; 8 (6) ArticleOpen Access

Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1–Associated Myelopathy and Correlates With Neuroinflammation

View ORCID ProfileCarolina Rosadas, Henrik Zetterberg, Amanda Heslegrave, Jana Haddow, Mina Borisova, Graham P. Taylor
First published October 5, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001090
Carolina Rosadas
From the Section of Virology (C.R., G.P.T.), Department of Infectious Disease, Imperial College London; UK Dementia Research Institute at UCL (H.Z., A.H., M.B.); Department of Neurodegenerative Disease (H.Z., A.H., M.B.) at UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and National Centre for Human Retrovirology (J.H., G.P.T.), St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
PhD
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Henrik Zetterberg
From the Section of Virology (C.R., G.P.T.), Department of Infectious Disease, Imperial College London; UK Dementia Research Institute at UCL (H.Z., A.H., M.B.); Department of Neurodegenerative Disease (H.Z., A.H., M.B.) at UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and National Centre for Human Retrovirology (J.H., G.P.T.), St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
Prof, MD, PhD
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  • For correspondence: henrik.zetterberg@clinchem.gu.se
Amanda Heslegrave
From the Section of Virology (C.R., G.P.T.), Department of Infectious Disease, Imperial College London; UK Dementia Research Institute at UCL (H.Z., A.H., M.B.); Department of Neurodegenerative Disease (H.Z., A.H., M.B.) at UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and National Centre for Human Retrovirology (J.H., G.P.T.), St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
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  • For correspondence: a.heslegrave@ucl.ac.uk
Jana Haddow
From the Section of Virology (C.R., G.P.T.), Department of Infectious Disease, Imperial College London; UK Dementia Research Institute at UCL (H.Z., A.H., M.B.); Department of Neurodegenerative Disease (H.Z., A.H., M.B.) at UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and National Centre for Human Retrovirology (J.H., G.P.T.), St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
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  • For correspondence: jana.haddow@nhs.net
Mina Borisova
From the Section of Virology (C.R., G.P.T.), Department of Infectious Disease, Imperial College London; UK Dementia Research Institute at UCL (H.Z., A.H., M.B.); Department of Neurodegenerative Disease (H.Z., A.H., M.B.) at UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and National Centre for Human Retrovirology (J.H., G.P.T.), St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
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  • For correspondence: m.borisova@ucl.ac.uk
Graham P. Taylor
From the Section of Virology (C.R., G.P.T.), Department of Infectious Disease, Imperial College London; UK Dementia Research Institute at UCL (H.Z., A.H., M.B.); Department of Neurodegenerative Disease (H.Z., A.H., M.B.) at UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and National Centre for Human Retrovirology (J.H., G.P.T.), St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
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Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1–Associated Myelopathy and Correlates With Neuroinflammation
Carolina Rosadas, Henrik Zetterberg, Amanda Heslegrave, Jana Haddow, Mina Borisova, Graham P. Taylor
Neurol Neuroimmunol Neuroinflamm Nov 2021, 8 (6) e1090; DOI: 10.1212/NXI.0000000000001090

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Abstract

Background and Objectives To evaluate the usefulness of CSF and plasma neurofilament light (Nf-L) as a biomarker for human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM).

Methods Nf-L, CXCL10, and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by single molecule array. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein, and HTLV-1 proviral load.

Results Nf-L was detected in all CSF samples (median [range] = 575 [791.8–2,349] pg/mL) and positively correlated with markers of inflammation (CXCL10 (r = 0.733), neopterin (r = 0.499), cell count (r = 0.403), and protein levels (r = 0.693) in CSF; p < 0.0015). There was an inverse correlation between Nf-L and duration of disease (r = −0.584, p < 0.0001). Wheelchair-dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin, and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10, and protein in CSF.

Conclusions Nf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuroinflammation.

Glossary

HAM=
HTLV-1–associated myelopathy;
HTLV-1=
human T-cell lymphotropic virus type 1;
Nf-L=
neurofilament light;
SIMOA=
single molecule array

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by the authors.

  • Received October 25, 2020.
  • Accepted in final form August 10, 2021.
  • Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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