Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis

• Published in: Multiple sclerosis Vol. 20; no. 10; pp. 1355 - 1362
• Main Authors: Amor, Sandra, van der Star, Baukje J, Bosca, Isabel, Raffel, Joel, Gnanapavan, Sharmilee, Watchorn, Jonathan, Kuhle, Jens, Giovannoni, Gavin, Baker, David, Malaspina, Andrea, Puentes, Fabiola
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.09.2014; Sage Publications Ltd
• Subjects: Adult; Antibodies, Monoclonal, Humanized - therapeutic use; Autoantibodies - blood; Biomarkers - blood; Case-Control Studies; Cross-Sectional Studies; Disability Evaluation; Drug Monitoring - methods; Enzyme-Linked Immunosorbent Assay; Europe; Female; Humans; Immunosuppressive Agents - therapeutic use; Longitudinal Studies; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive - blood; Multiple Sclerosis, Chronic Progressive - diagnosis; Multiple Sclerosis, Chronic Progressive - drug therapy; Multiple Sclerosis, Chronic Progressive - immunology; Multiple Sclerosis, Relapsing-Remitting - blood; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Natalizumab; Neurofilament Proteins - immunology; Predictive Value of Tests; Time Factors; Treatment Outcome; Europe; neurodegeneration; natalizumab treatment; Neurofilament light chain; antibodies; neuroinflammation; multiple sclerosis
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458514521887

Background: Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). Objective: To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. Methods: The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing–remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. Results: NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (p<0.001). NF-L antibody levels were lower in natalizumab treated than in untreated patients (p<0.001). In the longitudinal series, NF-L antibody levels decreased over time and a significant difference was found following 24 months of treatment compared with baseline measurements (p=0.001). Conclusions: Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS.