CXCL13, Inflammatory Marker, May Be Good at Predicting Likely MS Activity

CXCL13, an inflammatory biomarker, may be a good marker of likely future disease activity in people with multiple sclerosis (MS), a study suggests.

The study, “Intrathecally produced CXCL13: A predictive biomarker in multiple sclerosis,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.

Clinicians caring for people with MS need better molecular biomarkers to aid them in identifying patients at risk of disease progression and to help in its management.

CXCL13 — a known marker of inflammation — has been suggested as a potential prognostic biomarker for MS, as its levels are extremely high in patients.

Researchers at the Dartmouth Hitchcock Medical Center, in New Hampshire, examined the predictive value of CXCL13 in determining future disease activity in these people.

CXCL13 was compared to other biomarkers, namely: oligoclonal bands (OCBs), a measure of antibodies in the central nervous system, which is broadly indicative of inflammation; and neurofilament light (NfL), a biomarker of neuronal damage.

The study included 67 MS patients (mean age, 41.8) and 67 matched controls (mean age, 45) with non-inflammatory neurologic disease. Five patients with a follow-up of less than six months were excluded from the analyses; others were followed for about 2.5 years.

Patients presented different types of MS: 41 had clinically isolated syndrome (CIS), 13 had primary progressive MS (PPMS), eight had relapsing-remitting MS (RRMS), four had radiologically isolated syndrome (RIS), and one person had secondary progressive MS (SPMS).

The team analyzed protein levels in samples of blood and cerebral spinal fluid (CSF), the liquid surrounding the brain and spinal cord.

In MS patients, CXCL13 levels in the blood and CSF were significantly higher compared with controls. The CXCL13 index (ICXCL13) — a measure of intrathecal CXCL13 production; that is, CXCL13 in the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord — was also significantly higher in MS patients than in controls.

CXCL13 measures were then evaluated in MS patients with or without disease activity during follow-up. All CXCL13 levels in the blood were significantly lower in patients with positive activity than in those with inactive disease. In contrast, CXCL13 levels in the CSF and the CXCL13 index were high in the activity-positive patient group, compared with the activity-negative group.

Among all CXCL13 measures, ICXCL13 was found to be the best predictor of future disease activity in MS patients, and increased levels of ICXCL13 were observed across all disease subtypes compared with controls.

Additionally, a survival analysis showed a 20-month event free survival of 27% in ICXCL13-positive patients, compared to 82% in ICXCL13-negative patients. ICXCL13-positive patients were on average 7.5 times more likely to develop disease activity during follow-up.

As a single predictor, ICXCL13 outperformed both OCBs and CSF NfL in sensitivity, specificity, and predictive values for future disease activity in MS patients.

But combining ICXCL13 and CSF NfL status improved sensitivity and predictive values for disease activity. Of note, a positive correlation was found between ICXCL13 and CSF NfL levels in these patients.

“ICXCL13 may serve a role in routine clinical practice to assist clinicians in making treatment decisions in patients with MS including selecting optimal responders to therapy, determining therapeutic response, and identifying CIS or MS patients at a higher risk of inflammatory attacks who would benefit from immunomodulators,” the researchers wrote.

They noted several limitations to their study, including a limited follow-up period, a possible selection bias toward a restricted MS patient population, and findings of elevated ICXCL13 in other inflammatory neurological diseases.

Nonetheless, although further studies are necessary to fully evaluate the role of ICXCL13, “our present study identifies ICXCL13 as a single biomarker superior to both OCBs and CSF NfL in the prediction of future neuroinflammatory activity in MS patients,” the researchers concluded.