A lot of faith has been put into measuring neurofilaments, which are structural proteins of nerves as a marker of nerve damage. The idea is that as the nerve gets damaged it releases its contents and you have a marker for progression. However, the reality is that neurofilament light measurent perhaps is a better marker of inflammation induced damage. This floats around the cerebrospinal fluid and it then reaches the blood. The neurofilament can be measured in blood but there could be a problem and this is that neurofilaments are proteins that the immune systems does not normally see and so when it appears outside of nerves, anti-neurofilament antibodies can be made. If they bind to the bits of the neurofilaments that are used to detect them, then the neurofilament level may appear low. So are they a problem? Maybe DrLove, ProfG may want to come back to answer, as it is their work Maybe NDG will make an appearance..
Antibodies to neurofilament light as potential biomarkers in multiple sclerosis.Puentes F, Benkert P, Amor S, Kuhle J, Giovannoni G.BMJ Neurol Open. 2021; 3(2):e000192.
Background and objective: The concentration of neurofilament light (NfL) protein in cerebrospinal fluid (CSF) and blood is widely considered as a quantitative measure of neuro-axonal injury. Immune reactivity to NfL released into extracellular fluids induces specific autoantibody response. We investigated the levels and avidity of antibodies to NfL in patients with multiple sclerosis (MS) treated with disease-modifying therapies (DMTs) and their correlation with disease worsening and NfL protein concentration.
Methods: We conducted a prospective longitudinal study in 246 patients with MS (125 DMT-treated and 121 untreated at baseline). Serum levels of NfL antibodies, antibody avidity and immune complexes were determined by ELISA. NfL protein was measured using the Simoa platform.
Results: Levels of NfL antibodies were higher in progressive MS compared with clinically isolated syndrome (CIS)/relapsing remitting multiple sclerosis (RRMS) (p=0.010). Anti-NfL levels drop with increasing disability score (Expanded Disability Status Scale (EDSS)) (p=0.002), although conversely, were significantly elevated in CIS/RRMS after a recent EDSS increase (p=0.012). Patients receiving DMTs showed decreased levels of anti-NfL (p=0.008), high-avidity antibodies (p=0.017) and immune-complexes compared with untreated CIS/RRMS. Patients with MS switching to natalizumab showed lower levels of anti-NfL but higher immune complexes compared with healthy controls (p=0.0071). A weak association was observed between the levels of NfL protein and NfL antibodies.
Conclusions: These results support the potential usefulness of quantifying antibody response to NfL as potential markers of progression and treatment response in MS and need to be considered when interpreting peripheral blood NfL levels.
However, dont hold your breath. Maybe we could devise a test that avoids these issues but fear not they can detect neurofilament and antibodies in complex
General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry, nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. Please note that Professor Gavin Giovannoni has no responsibility for this blog.