• systemic vasculitis
• autoimmune diseases
• disease activity
• granulomatosis with polyangiitis
• sjoegren’s syndrome

Peripheral nerve biopsy remains the gold standard for diagnosing vasculitic neuropathy (VN).1 This procedure is invasive, of limited sensitivity and not always feasible.2 A biomarker indicating acute axonal loss in patients with systemic vasculitis would allow rapid screening and adjustments of diagnostic or treatment strategies, potentially improving clinical outcome.3

Neurofilaments are structural proteins specific to neurons that are released into blood and cerebrospinal fluid following neuronal damage. They have been suggested as a biomarker in various neurological diseases, mainly affecting the central nervous system.4–6 In patients with multiple sclerosis, serum neurofilament light chain (sNfL) levels correlated with MRI and clinical disease activity/severity, were lower in patients under treatment and showed potential to predict future disease activity and disability.5

In this retrospective study we aimed to test whether sNfL could serve as a marker of vasculitic damage of peripheral nerves and/or disease activity in patients with VN. Patients were recruited from our prospective local ethical board-approved vasculitis cohort. VN was diagnosed by biopsy or, in case biopsy was declined or yielded indefinite results, by clinical presentation.1 Neurological disability was assessed using the Medical Research Council Sum Score, measuring motor function of 12 key limb muscles (normal exam at maximum score 60), and the Neurological Symptom Score, scoring cranial nerve deficits, motor function, positive and negative sensory and autonomic symptoms (maximum disability at score of 17).7 8 Systemic vasculitic disease activity was determined by the Birmingham Vasculitis Activity Index.9 VN remission was defined as stable or improved neurological exam.

sNfL levels were determined by a novel ultrasensitive Simoa5 assay in a 10-patient cohort at initial presentation with active VN and subsequent remission (table 1). Serial samples were available before onset of neuropathy in one cohort patient (patient 8) and an additional relapsing patient (patient 11).

sNfL levels at diagnosis were compared with 30 age-matched and sex-matched healthy controls (HC), 10 age-matched controls at diagnosis of systemic vasculitis without neuropathy (VC) and 3 patients with non-vasculitic neuropathy (NC) (diabetic, idiopathic and paraneoplastic, respectively).

At the time of sampling, all patients of the VN and VC groups had active disease. sNfL levels were higher in the VN patients at diagnosis (median 215; range 74–2364 pg/mL) compared with HC (median 29; range 10–64 pg/mL, p<0.001), NC (median 64; range 34–73 pg/mL, p~0.028) and VC (median 43; range 15–147 pg/mL, p<0.001) (figure 1A). At VN diagnosis sNfL levels were significantly higher than during remission (median 57; range 12–83 pg/mL; p=0.002) (figure 1B). In patients 8 and 11 (table 1) sNfL levels clearly paralleled clinical course before VN onset (patient 8) and relapse (patient 11), respectively, and during active disease and remission (figure 1C).

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Figure 1

(A) Median sNfL levels in patients with vasculitic neuropathy at diagnosis (VN diagnosis) and during remission (VN remission), healthy controls (HC), patients with vasculitis without neuropathy (VC) and patients with non-vasculitic neuropathy (NC) (whiskers indicate IQR range). (B) Longitudinal measurement of sNfL levels at diagnosis and during remission in patients with vasculitic neuropathy and (C) sNfL levels for VN patient 8 (circle) before, at onset and in remission, and patient 11 (diamond) during remission, at relapse and during subsequent remission. Pairwise Wilcoxon rank-sum test was performed. Holm correction was applied to correct for multiple comparisons. sNfL, serum neurofilament light chain.

Applying an sNfL cut-off value of 155 pg/mL, the sensitivity and specificity to classify correctly between active VN versus VC or NC were 82% and 100%, respectively (area under the receiver operating characteristic curve (AUC) 0.96). There was no difference in sNfL levels between VN at FU and NC, VC or HC (p~0.11).

These data support sNfL as a promising marker to (1) correctly identify patients with VN and to (2) assess VN disease activity, as suggested by the profound decline of sNfL levels during remission. The high specificity of sNfL to axonal damage might be due to the high expression of NfL in large myelinated axons,4 which are predominantly affected in VN.10

This study is limited by its retrospective nature and relatively low number of included individuals. Nevertheless our data suggest sNfL as a biomarker in diagnosis and monitoring of VN and merit further confirmation in a prospective study.