51成人动漫

Serum (NF-L) could become a biomarker for identifying subclinical activity and treatment response in relapsing-remitting MS (RRMS), signalling the need for MRI, researchers said.

In a cohort of 85 patients with relapsing-remitting MS (RRMS), 2-year follow-up results showed that levels of this serum protein were significantly higher in patients with MRI-confirmed subclinical disease activity and lower after patients received disease-modifying treatment, according to Kristin N. Varhaug, MD, of Haukeland University Hospital in Bergen, Norway, and colleagues.

A serum NF-L increase of 10 pg/ml was associated with a 48% increased risk of new T1 gadolinium-enhancing lesion development and a 62% increased risk of a new T2 lesion, they reported online in .

"According to our data, rising NF-L levels, with or without clinical symptoms, may act as a trigger for MRI scanning," the researchers wrote. "Therefore, patients with stable clinical course and stable NF-L levels may be spared unnecessary, and costly, MRI scans. This needs to be confirmed in larger prospective patient populations."

NF-L levels were significantly higher in patients with new T1 lesions as well as in those with new T2 lesions (both 37.3 pg/mL) compared with those without new lesions (28.0 pg/mL, β=1.258, P<0.001 and 27.7 pg/m, β=1.251; P<0.001, respectively).

NF-L levels were also associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (P<0.001) and 1 month after (P=0.009) serum biomarker measurement. Following initiation of IFNB-1a treatment, there was a drop in NF-L levels (P<0.001), the study showed.

"These blood tests could provide a low-cost alternative to MRI for monitoring disease activity," Varhaug noted in a statement.

Study participants received 18 months of treatment with interferon-beta 1a (IFNB-1a) and went without disease-modifying treatment for 6 months. All had a monthly MRI for the first 9 months of the study, then again at the end of year 1 and year 2. Serum samples were taken at baseline and repeated at 3 and 6 months and then after years 1 and 2.

The researchers used a single-molecule array assay to analyze serum levels of NF-L and mixed-effects models to estimate the association with clinical and MRI disease activity.

A second biomarker -- chitinase 3-like 1 (CHI3L1) -- did not appear to be predictive of subclinical disease activity in RRMS. There was no association between changes in CHI3L1, also known as YKL 40, and clinical or MRI disease activity or treatment with interferon-beta 1a, the researchers said.

Associations between serum NF-L and subclinical disease activity and reduction in NF-L levels after starting INFB-1a treatment support linking serum NF-L levels to disease activity in multiple sclerosis (MS), Varhaug's group pointed out. Another study showed that serum NF-L was a sensitive and clinically useful biomarker for monitoring tissue damage and , and was correlated with NF-L levels in cerebrospinal fluid.

"This assay -- if it proves to be reliable and reproducible, and I think it will -- could be another way of measuring subclinical disease activity," said Jerry S. Wolinsky, MD, of the University of Texas McGovern Medical School in Houston.

It may be even more informative about subclinical disease activity in patients with primary progressive disease, potentially allowing clinicians to better control both relapsing and progressive forms of MS, Wolinsky, who was not involved in the study, told 51成人动漫.

"At this time, neurofilament light analysis represents our best chance at having a validated fluid biomarker," said Fred D. Lublin, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

"More studies will determine how this assay will be most useful," added Lubin, who is co-chief editor of Multiple Sclerosis and Related Disorders. He was not affiliated with the current study.

This study's well-characterized clinical cohort had frequent MRI which allowed researchers "to really compare the time course over which serum NF-L levels correlated with radiologic measures of MS activity," noted Erin Longbrake, MD, PhD, of the Yale School of Medicine in New Haven, Connecticut.

"That information should help to improve the design of future clinical trials," Longbrake, who was not involved in the study, told 51成人动漫.

Although NF-L may prove useful for measuring disease progression or disease activity in MS clinical trials, however, Longbrake doubted it would replace MRI as an individual level biomarker.

"There was a great deal of overlap in the NF-L levels of patients with and without disease activity," she pointed out. "Thus, even though NF-L was significantly correlated with disease activity on average, there was no cut-point that distinguished 'normal' from 'abnormal' levels for an individual. This would make the test difficult to apply in a clinical setting."

Wolinsky also said he didn't think the serum biomarker would ever completely replace MRI for monitoring disease activity and treatment response in RRMS. However, it could augment the information that clinicians have when ordering an MRI, he said.

Currently, clinicians are advised to order an annual MRI in every MS patient, he pointed out. "Maybe MRI can be done less often. These kinds of answers will be forthcoming soon."

The biomarker may have other applications, such as monitoring acute or chronic damage to the central nervous system.

"Since it's a marker of axonal injury, it could be used to follow an NFL player who has had a traumatic head injury for signs of traumatic encephalopathy, Parkinson's disease, or Alzheimer's," Wolinksy said. In the patient with MS, the marker could potentially differentiate head injury sustained in a car accident, for example, from relapse.

Comment