Image: The Neurofilament light (NF-L) ELISA allows fast quantification in less than three hours of NF-L in cerebrospinal fluid (Photo courtesy of UmanDiagnostics).
Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS) in which neuronal damage is present at an early stage. Due to both unpredictable and heterogeneous disease course and treatment response, biomarkers reflecting these processes are highly sought after.
A blood test to monitor a nerve protein in the blood of people with multiple sclerosis (MS) may help predict whether disease activity is flaring up. The nerve protein, called neurofilament light chain (NF-L), is a component of nerve cells and can be detected in the blood stream and spinal fluid when nerve cells die.
Scientists at the University of Bergen (Bergen, Norway) and their collaborators enrolled a cohort of 85 patients with relapsing-remitting MS (RRMS) were followed for two years; six months without disease-modifying treatment and 18 months with interferon-beta 1a (IFNB-1a). Serum samples were collected at baseline and months 3, 6, 12, and 24 and magnetic resonance imaging (MRI) was performed at baseline and monthly for 9 months and then at months 12 and 24.
The team analyzed the serum levels of NF-L using a single-molecule array assay and chitinase 3-like 1 (CHI3L1) by enzyme-linked immunosorbent assay (ELISA) and estimated the association with clinical and MRI disease activity using mixed-effects models. The concentration of NF-L was determined using a Simoa assay. The concentration of CHI3L1 in serum was measured using an ELISA.
The scientists reported that nerve protein levels in the blood were higher when MRI detected new T1 and T2 lesions, which are areas of damage in the brain due to MS. Those with new T1 lesions had 37.3 pg/mL of the nerve protein in their blood compared with 28 pg/mL for people without new T1 lesions. Those with new T2 lesions had 37.3 pg/mL of nerve protein in the blood compared with 27.7 pg/mL for those without new T2 lesions. Increased nerve protein levels were present for a three-month time period during the development of new lesions. Nerve protein levels also fell when treatment with interferon-beta 1a treatment began. The team found that an increase of 10 pg/mL in a person was associated with a 48% increased risk of developing a new T1 lesion and 62% increased risk of a new T2 lesion. Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.
Kristin N. Varhaug, MD, the lead author of the study, said, “Since MS varies so much from person to person and is so unpredictable in how the disease will progress and how people will respond to treatment, identifying a biomarker like this that can help us make predictions would be very helpful. These blood tests could provide a low-cost alternative to MRI for monitoring disease activity.” The study was published on November 29, 2017, in the journal Neurology - Neuroimmunology Neuroinflammation.
University of Bergen