Analysis of TWEAK Protein Levels May Help Identify Active Inflammation in MS Patients, Study Suggests

High blood levels of a signaling protein known as TWEAK are associated with active neuroinflammation in patients with multiple sclerosis (MS), a study shows.

This finding suggests that TWEAK may be a valuable biomarker to assess ongoing inflammation and overall MS activity, and potentially help optimize patient care.

The study, “High levels of serum soluble TWEAK are associated with neuroinflammation during multiple sclerosis,” was conducted by a French research team, and published in the Journal of Translational Medicine.

MS is an immune-mediated neurological disorder characterized by progressive degeneration of nerve cells. Deregulation of immune cells with overactivation of pro-inflammatory responses is a core mechanism involved in MS development and progression.

Management and prevention of MS symptoms is mainly achieved by controlling the related inflammatory processes, and inhibiting their damaging effect on nerve cells. However, the effectiveness of these treatment strategies depends, to a great extent, on the right timing. So, finding biomarkers that can help monitor the disease status and its inflammatory activity are of great interest to the scientific and clinical MS communities.

TWEAK is a signaling protein that can mediate inflammatory responses in the central nervous system. It is produced and secreted by circulating immune cells but also by microglia, the immune cells resident in the brain.

Studies have suggested that TWEAK protein may contribute to the neuroinflammatory process in the MS brain.

To further explore the potential role of this protein in MS, researchers evaluated its levels in blood samples of 28 patients after a first clinical episode suggestive of MS, and 57 healthy volunteers.

At the beginning of the study, blood levels of TWEAK were 2.3 times higher in MS patients than healthy controls — mean 1,086 pg/mL versus 467 pg/mL. However, the levels of the protein were not associated with an increase in serum C reactive protein, which is a commonly used biomarker of systemic inflammation, or monocyte (a type of immune cell involved in MS) numbers.   

Follow-up analysis at six and 12 months after disease onset revealed that TWEAK blood levels, in general, decreased over time, but they remained higher in MS patients than in the control group.

During the first year after disease onset, the team collected a total of 84 blood samples, of which 39 were taken during clinical relapse. Analysis of this particular group of samples revealed that TWEAK levels were 1.5 times higher during relapses, compared with samples collected in non-relapse periods — mean 935 pg/mL versus 611 pg/mL.

Further analysis revealed that patients who had active lesions, as determined by gadolinium-enhanced magnetic resonance imaging (MRI) scans, had significantly increased levels of TWEAK than patients without lesions.

Notably, the team did not find a correlation between TWEAK levels and short-term brain tissue damage, which suggests that the protein may not directly contribute to the neurodegeneration processes.

These findings suggest that “TWEAK is mainly a biomarker of inflammation in MS,” the researchers wrote.

Additional studies are still warranted to better understand the long-term stability of the protein, and validate its potential as a biomarker of active neuroinflammation.

TWEAK analysis “is a simple and reproducible serum test that could be proposed as an accurate marker of ongoing inflammation, contributing to the follow-up and the care of MS patients,” the researchers concluded.