Key Points
• Source: BMJ Neurology Open
• Conclusion/Relevance: “These results support the potential usefulness of quantifying antibody response to NfL [neurofilament light] as potential markers of progression and treatment response in MS and need to be considered when interpreting peripheral blood NfL level.”
• The levels of neurofilament light (NfL) protein in cerebrospinal fluid (CSF) and blood are a biomarker of neuro-axonal injury. Immune reactivity to NfL released into extracellular fluids triggers autoantibody responses, which were investigated by the researchers. Specifically, they looked at the avidity of antibodies to NfL in MS patients administered disease-modifying therapies (DMTs), as well as the link between disease worsening and NfL protein concentrations. They discovered that concentrations of NfL protein weakly correlated with the levels of NfL specific antibodies, as well as noting a trend for an inverse correlation between these factors and recent relapse.
• “High-frequency sampling data would be needed to study the dynamic of the different parameters and a possible lag-time needed to allow the expansion of specific humoral response once NfL is released,” wrote the authors.
• Researchers found that antibody levels vs NfL usually heightened with age in those with MS. They noted a negative correlation between the level of NfL antibodies and the Expanded Disability Status Scale (EDSS), which could be secondary to low-avidity NfL antibodies considering a paucity of association of EDSS with the antibody avidity.
• “In contrast, a significant positive association between the incidence of NfL antibodies and a recent EDSS increase was found. Of note in patients with RRMS [relapsing remitting multiple sclerosis], a recent EDSS increase was correlated with augmented levels of total NfL antibodies but not associated with their avidity, which can be related to the time needed for affinity maturation to occur. This suggests a possible protective role of NfL antibodies or a cumulative effect in PPMS/SPMS [primary progressive multiple sclerosis/secondary progressive multiple sclerosis] in contrast with an actual inflammatory process in active RRMS that seems to be reflected in an EDSS increase,” wrote the authors.
• The relationship between higher NfL antibody levels and an increase in EDSS may indicate recent neuronal damage, where the measurement of NfL antibodies could serve as a biomarker for diagnosis and progression.