Serum Neurofilament Light Chain Levels in Leprosy Patients: A Cross-Sectional Study

BACKGROUND:

Leprosy causes nerve damage which may be clinical or subclinical. Leprosy-associated peripheral neuropathy (LPN) has an unpredictable course despite treatment with multi drug therapy, and results in significant disabilities and stigma. There are no reliable biomarkers to quantify nerve damage in leprosy or predict impending clinical neuropathy.

METHODS:

We conducted a cross-sectional observational study over 1 year. Leprosy patients with peripheral neuropathy (LPN, n = 30), leprosy patients without detectable peripheral neuropathy (L, n = 20) and healthy controls (HC, n = 20) were included. Patients with other known causes of peripheral neuropathy were excluded. The primary outcome was to estimate serum neurofilament light chain (NfL) levels using the Single Molecular Assay (SiMoA) HD-X analyzer. NfL concentrations were compared across the three groups and correlated with disease spectrum, bacterial load and severity of nerve function impairment (NFI).

RESULTS:

The median NfL level in the LPN group was 12.1 pg/mL (range: -1.68 to 224), in the L group was 17.25 pg/mL (range: 4.43-53.8) and in HCs was 4.85 pg/mL (range: 0.252-23.7). Leprosy patients had significantly higher NfL levels than healthy controls (p = 0.008), with a cut-off value of 7.48 pg/mL using ROC analysis (sensitivity 76%; specificity 25%). NfL levels between the LPN and L groups were comparable (p = 0.56). No significant correlation was found between NfL levels and severity of clinical neuropathy, although a non-significant positive trend with the bacterial index was noted.

CONCLUSIONS:

Serum NfL levels were significantly higher in leprosy patients compared to healthy controls, suggesting prominent axonal damage. NfL may serve as a minimally invasive biomarker of nerve damage in leprosy, but further longitudinal studies are needed to validate its predictive and therapeutic utility in LPN.