Investigation of serum neurofilament light chain as a biomarker in Fabry disease

• Published in: Scientific reports Vol. 14; no. 1; pp. 23033 - 9
• Main Authors: Ponleitner, Markus, Gatterer, Constantin, Bsteh, Gabriel, Rath, Jakob, Altmann, Patrick, Berger, Thomas, Graf, Senta, Sunder-Plassmann, Gere, Rommer, Paulus Stefan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/2489/1512; 631/378/1689/534; 692/617/375/1370/534; 692/699/317; Adult; Aged; Biomarkers; Biomarkers - blood; Body mass index; Case-Control Studies; Central nervous system; Cerebrovascular disorders; Creatinine; Fabry disease; Fabry Disease - blood; Fabry Disease - diagnosis; Fabry's disease; Female; Glomerular filtration rate; Humanities and Social Sciences; Humans; Ischemia; Light chains; Lysosomal storage diseases; Male; Middle Aged; multidisciplinary; Neurofilament light; Neurofilament Proteins - blood; Renal function; Science; Science (multidisciplinary); Severity of Illness Index; Substantia alba; Tau protein; Young Adult; Fabry disease; Neurofilament light; Biomarkers; Cerebrovascular disorders; Glomerular filtration rate
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-73537-y

Fabry disease (FD) constitutes a rare, X-linked lysosomal storage disorder affecting multiple organ systems, most notably heart, kidneys, and the central nervous system. Neurofilament light chains (NfL) have emerged as a prime candidate for a body fluid biomarker reflecting neuro-axonal injury. We aimed to evaluate its addition to the diagnostic and monitoring armamentarium in FD. Serum NfL concentrations (sNfL) were measured in 50 people with FD (PwFD) and 30 healthy control subjects (HC) using the Simoa© technology, followed by calculation of Z-scores adjusted for age and body mass index. In addition, clinical disease severity in PwFD was measured using the FOS-MSSI (Fabry outcome study – Mainz severity score index), which comprises clinical and paraclinical parameters. PwFD show elevated sNfL Z-scores compared to HC (PwFD: 1.12 [SD 1.5], HC: 0.01 [SD 1.2], p  < 0.001). In PwFD, males showed higher sNfL Z-scores than females (1.75 [SD 1.5] vs. 0.73 [SD 1.4]). Importantly, sNfL Z-scores were increased in PwFD with ischemic white matter lesions of the CNS (1.5, SD 2.2 vs. 0.5, SD 2.9, p  = 0.03). In our small cohort, sNfL Z-scores correlated fairly with FOS-MSSI (Kendall’s-Tau [τ] = 0.25, p  = 0.01), and, interestingly with serum creatinine (τ = 0.28, p  = 0.005) and estimated glomerular filtration rate (eGFR, τ =-0.28, p  = 0.005). Based on these exploratory results, sNfL might provide value as a biomarker of neuroaxonal damage in FD, possibly reflecting cerebrovascular injury. Additionally, the correlation of sNfL with renal function warrants further investigation.