Protein levels in CSF may help diagnose primary progressive MS

The level of proteins called kappa free light chains in the cerebrospinal fluid (CSF) — the liquid that surrounds the brain and spinal cord — may be used as a diagnostic marker to identify the presence of primary progressive multiple sclerosis (MS), according to a new study.

Testing for these proteins worked just as well as measuring oligoclonal bands, or bands of antibodies indicative of inflammation that can be seen when a patient’s CSF is analyzed in the lab.

“We provide profound evidence that [kappa free light chains] index and [oligoclonal bands testing] show similar diagnostic performance in patients with [primary progressive] MS and, thereby, filled the prior scientific and practical gap in this field,” the researchers wrote.

Indeed, the team said kappa free light chains “are an emerging biomarker.”

The study, “Diagnostic value of kappa free light chain index in patients with primary progressive multiple sclerosis – a multicentre study,” was published as a brief article in Frontiers in Immunology.

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August 29, 2023 News by Marisa Wexler, MS

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Kappa free light chains testing worked as well as another measure

The diagnosis of MS typically involves a combination of clinical history, neurological examination, imaging studies (such as magnetic resonance imaging or MRI), and  laboratory tests — including CSF analysis.

Oligoclonal banding is a specific test performed on the CSF to identify abnormal bands of antibodies, specifically IgG, which may indicate an inflammatory or immune response within the central nervous system, which is comprised of the brain and spinal cord. While oligoclonal bands are not exclusive to MS, their presence in the CSF can be supportive evidence for a diagnosis.

It is now known that kappa free light chains also build up in the CSF when the brain and spinal cord become inflamed. A recent meta-analysis showed that measuring kappa free light chains may be important in the diagnostic workup of people with suspected MS. However, most studies were done in people with relapsing-remitting MS (RRMS).

In RRMS, periods of new or worsening symptoms, often called relapses or flares, are followed by periods of remission in which symptoms ease. Conversely, in primary progressive MS, also called PPMS, patients experience gradual worsening of MS symptoms over time without such periods of remission.

Now, a team of researchers in Europe sought to find out how well kappa free light chains worked to identify people with PPMS.

Their study included 174 people — 88 men and 86 women — with primary progressive MS who were recruited through 11 MS centers across seven European countries. Their mean age was 52.

A kappa free light chain index was calculated based on the levels of these proteins in the CSF and blood. Their measure also took into account the levels of albumin, the most abundant protein in the blood. An index greater than 6.1 was deemed positive.

The median kappa free light chain index was 54.6 and significantly correlated with the number of white blood cells in the CSF, as well as with the levels of IgG.

The index was positive in 161 patients (93%), whereas oligoclonal bands were positive in 153 (88%). The two tests were in agreement in the vast majority (90%) of the cases.

By showing high diagnostic performance independent of the initial MS disease courses, [assessing kappa free light chains]  might serve as alternative to [oligoclonal band] testing in patients with suspected MS.

Even across centers, the test’s sensitivity was 93%. Sensitivity refers to how well the kappa free light chain index can identify primary progressive MS in patients who actually have the disease.

Measuring kappa free light chains in the CSF is fast and cost-effective, the team noted.

Overall, the researchers said, the kappa free light chains index “shows similar diagnostic sensitivity” to oligoclonal band testing in PPMS.

“By showing high diagnostic performance independent of the initial MS disease courses, it might serve as alternative to [oligoclonal band] testing in patients with suspected MS,” the researchers concluded.