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Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis
  1. Fabiola Puentes1,
  2. Joanne Topping1,
  3. Jens Kuhle1,
  4. Baukje J van der Star2,
  5. Abdel Douiri3,
  6. Gavin Giovannoni1,
  7. David Baker1,
  8. Sandra Amor1,2,
  9. Andrea Malaspina1,4
  1. 1Neuroimmunology Unit, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  2. 2Department of Pathology, VU University Medical Center and MS Center, Amsterdam, The Netherlands
  3. 3Department of Public Health Sciences, King's College London & NIHR Biomedical Research Centre, London, UK
  4. 4North-East London and Essex MND Regional Care Centre, London, UK
  1. Correspondence to Dr Fabiola Puentes, Neuroimmunology Unit, Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK; f.puentes{at}qmul.ac.uk

Abstract

Background Neurofilament (NF) proteins detection in biological fluids as a by-product of axonal loss is technically challenging and to date relies mostly on cerebrospinal fluid (CSF) measurements. Plasma antibodies against NF proteins and particularly to their soluble light chain (NF-L) could be a more practical surrogate marker for disease staging in amyotrophic lateral sclerosis (ALS), an invariably fatal and clinically heterogeneous neuromuscular disorder.

Methodology We have used a recombinant neurofilament light chain (NF-L) protein for the ELISA detection of antibodies against NF proteins in plasma samples from a well-characterised cohort of ALS individuals (n:73). The use of an established functional rating scale and of a recently proposed staging of disease progression allowed stratification of the ALS cohort based on disease stage, site of onset, survival and speed of disease progression.

Results Antibody levels to NF proteins in plasma were significantly higher in ALS individuals compared to healthy controls (p<0.001). Higher NF plasma immunoreactivity was seen in advanced ALS cases (stage IVA-B) compared to earlier phases of the disease (p<0.05). There was no difference in anti-NF plasma antibodies between ALS individuals treated with riluzole and untreated patients; although riluzole-treated ALS cases with an earlier age of onset and with a shorter diagnostic delay displayed higher anti-NFL antibody levels compared to untreated ALS patients with similar features.

Conclusions Immunoreactivity to plasma NF-L and homologous NF proteins is informative of the stage of disease progression in ALS. The determination of NF antibody levels in plasma could be added to the growing panel of disease-monitoring biomarkers in ALS targeting cytoskeletal antigens.

  • ALS

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