Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis.
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.
['Puentes|Fabiola|F|', 'Topping|Joanne|J|', 'Kuhle|Jens|J|', 'van der Star|Baukje J|BJ|', 'Douiri|Abdel|A|', 'Giovannoni|Gavin|G|', 'Baker|David|D|', 'Amor|Sandra|S|', 'Malaspina|Andrea|A|']
D000368:Aged D000690:Amyotrophic Lateral Sclerosis D000906:Antibodies D015415:Biomarkers D016022:Case-Control Studies D018450:Disease Progression D004797:Enzyme-Linked Immunosorbent Assay D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D016900:Neurofilament Proteins D018696:Neuroprotective Agents D011994:Recombinant Proteins D019782:Riluzole
ALS