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New biomarker may predict progression to MS (06/01/17)

Cerebrospinal fluid levels of soluble CD27 may predict progression from clinically isolated syndrome (CIS) to multiple sclerosis, researchers reported.

In a Dutch study of 77 CIS patients, CSF levels of soluble CD27 were predictive of an MS diagnosis (HR 2.4 per 100 U/mL increase in sCD27 levels, P=0.007), according to Rogier Hintzen, MD, PhD, of Erasmus Medical Center in Rotterdam in the Netherlands, and colleagues.

The biomarker also predicted worse disease - those who progressed to MS and had higher baseline levels of soluble CD27 when diagnosed with CIS had a 5.5-fold higher annualised relapse rate than those with lower levels (0.33 versus 0.06, P=0.02), they reported online in JAMA Neurology.

"CSF sCD27 could be an activation marker directly related to the immunopathology of the disease, with potential value for selecting patients with higher subsequent disease activity," the researchers wrote.

CD27 is a membrane glycoprotein tumor necrosis factor family receptor that is released by activated T lymphocytes and thus is a marker of T-cell activation and inflammation, the authors explained.

Other tools for predicting progression from CIS to MS include the gold-standard of the number of T2 lesions on brain MRI at the time of CIS diagnosis, with a larger number of T2 lesions being tied to a shorter time to MS diagnosis. CSF levels of oligoclonal bands (OCBs), which are clonally expanded IgGs that are thought to reflect an intrathecal humoral immune response, also have some utility in predicting progression to MS, they said.

Good prediction of progression is needed in order to better manage patients, the researchers said. Currently, disease-modifying therapy is routinely offered to patients with CIS who have high-risk features, but these drugs have side effects and it's important to avoid unnecessary treatment, they wrote.

To evaluate an additional potential biomarker, Hintzen's group studied 77 patients who were diagnosed with CIS from March 2002 to May 2015 in a tertiary referral center: 80% were female and the mean age was 33. All of them had a lumbar puncture and an MRI within 6 months of symptom onset. Control patients who'd had a lumbar puncture at the center during that time for some other reason also had a mean age of 33, and 67% were female.

Patients with CIS had higher CSF levels of sCD27 than controls (mean 31.3 U/mL versus 4.7 U/mL, P<0.01), and only about 11% of CIS patients received disease-modifying drugs, either glatiramer acetate or interferon beta.

During a mean follow-up of 55 months, 51% of the patients were diagnosed with MS.

The researchers found that sCD27 levels were significantly increased in those who progressed to MS compared with those who did not (42 U/mL versus 23.2 U/mL, P=0.03), and those with higher levels had a shorter time to MS diagnosis than those with lower levels.

In a model adjusted for MRI and CSF measurements, sCD27 levels were significantly associated with a diagnosis of MS (HR 2.4 per 100 U/mL increase in sCD27 levels, P=0.007). They were also tied to more severe disease, with a 5.5-fold higher annualised relapse rate than those with low levels.

The study was limited in that the sample size was sufficient for multivariate analysis, but still needs validation in a bigger cohort. Regardless, the researchers concluded that the study suggests sCD27 "could be an activation marker directly related to the immunopathology of the disease, with potential value for selecting patients with higher subsequent disease activity."

In an accompanying editorial, Jeffrey Gelfand, MD, of the University of California San Francisco, noted that the history of CD27 in MS "has a long arc." Early on, CD27 levels in serum didn't discriminate normal patients from those with MS. But in 2015, a computer program found that CSF CD27 was the most powerful single biomarker for discerning neuroimmunological disease from non-inflammatory neurological disease and healthy controls.

"Unfortunately, there is a rub, and that is that CSF sCD27 levels appear to be highly correlated with oligoclonal bands, IgG index, and baseline MRI fluid-attenuated inversion recovery/T2 abnormalities in the CIS population," Gelfand wrote. "In other words, high CSF sCD27 is present in the same patients who already have high-risk MRI findings and oligoclonal bands."

"It is possible that study in larger CIS cohorts will find that elevated sCD27 is associated with increased MS risk even when MRI is negative or oligoclonal bands are negative, but this remains to be demonstrated," he wrote. "For now, MRI and oligoclonal bands will remain the mainstay of risk stratification in CIS."

Source: MedPage Today © 2017 MedPage Today, LLC (06/01/17)

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