Neurofilament light chain as a marker of peripheral nerve damage in vasculitic neuropathy? A cross-compartmental correlation analysis in patients undergoing nerve biopsy.

Vasculitic neuropathy remains challenging to diagnose and monitor because of its heterogeneous clinical and laboratory presentation. Blood-based biomarkers indicating nerve damage could serve as an additional diagnostic tool to ensure early diagnosis, precise therapeutic monitoring, and a more targeted anti-inflammatory treatment. A potential marker for this purpose is neurofilament light chain (NfL), a marker of neuroaxonal damage that is used as a biomarker in several diseases of the central and peripheral nervous system. NfL has also been suggested to reflect disease activity in patients with vasculitic neuropathy. However, its biodynamics and link to degeneration of peripheral nerve tissue remain unconfirmed. To investigate the usefulness of NfL as a marker of peripheral nerve damage in this context, we retrospectively assembled a cohort of 35 patients undergoing sural nerve biopsies (including patients with vasculitic neuropathy and other neuropathies). We then measured NfL in serum samples cryoarchived at the time of biopsy and correlated NfL levels with histological parameters. For our histological analysis, we quantified parameters of acute axonal degeneration and chronic axonal loss using a combination of manual, threshold-based, and supervised learning-based analyses. We found a significant positive correlation between parameters of acute axonal degeneration and serum-NfL levels that persisted after adjusting for age and concomitant central nervous system disease. We did not find a similar correlation with parameters of chronic axonal loss quantified in nerve biopsies. These findings support the value of NfL as a marker for acute axonal degeneration in patients with vasculitic neuropathy.