Summary
An international panel of experts recommended including the determination of intrathecal kappa free light chain (κ-FLC) synthesis in the next revision of MS diagnostic criteria. The κ-FLC index, easily determined by nephelometry and turbidimetry, is a fast, cost-effective, and quantitative biomarker with high diagnostic value for MS. It also predicts future inflammatory disease activity and disability progression, making it a valuable prognostic tool.
Amy Carpenter
An international panel of experts in multiple sclerosis and cerebrospinal fluid diagnostics reached a consensus in 2023, and they recommended including the determination of intrathecal kappa free light chain synthesis in the next revision of MS diagnostic criteria as an additional tool to measure intrathecal immunoglobulin synthesis (Hegen H, et al. Mult Scler. 2023;29[2]:182–195).
κ-FLC is easily determined by nephelometry and turbidimetry. “We have an easy, fast, labor-saving method that is cost-effective. We have a stable analyte with a high diagnostic value, and the result we get is rater-independent and quantitative,” Harald Hegen, MD, PhD, of the Department of Neurology, Medical University of Innsbruck, Austria, said of κ-FLC. He is one of the panel’s dozen members whose aim was to evaluate and recommend the type of CSF analysis that yields the greatest sensitivity and specificity in the diagnosis of MS.
Last year, in the newly published revisions of the McDonald criteria for MS diagnosis, was the following: The κ-FLC index is an appropriate paraclinical test for the diagnosis of MS, and it is interchangeable with, and can substitute for, oligoclonal bands (Montalban X, et al. Lancet Neurol. 2025;24[10]:850–865).
“Why do we need a new biomarker?” Dr. Hegen asked in his ADLM presentation last summer. The IgG index is fast and easy, he said, but it has a moderate diagnostic sensitivity of only 60 to 70 percent. Oligoclonal banding has a high sensitivity but is labor-intensive and rater-dependent, and it provides only a positive or negative result. (See “Close-up on traditional lab biomarkers for MS,” https://bit.ly/CT_0226_MS.)
In addition to its diagnostic value, κ-FLC also has prognostic value, Dr. Hegen said, “as the kappa free light chain index predicts future inflammatory disease activity and disability progression.”
Evidence of an intrathecal IgG synthesis in the CSF proves the inflammatory nature of MS and increases diagnostic certainty, Dr. Hegen said, and “the gold standard in the last decade to detect an intrathecal IgG synthesis was the detection of CSF-restricted oligoclonal bands.”
Besides intact immunoglobulins, terminally differentiated B cells (plasma cells) produce light chains in excess, and they are secreted freely. The two isotopes are kappa free light chains and lambda free light chains. It is in the κ-free light chains that “we have the profound evidence of MS,” he said.
κ-free light chains behave similarly to immunoglobulins. “So we can find immunoglobulins and free light chains in the blood compartment, and on the physiological connotations they are passively transferred all throughout the CSF compartment.”
In case of an inflammatory disease of the central nervous system like MS, Dr. Hegen said, “we have in addition an intrathecal production of immunoglobulins, but we also have an intrathecal production of kappa free light chains,” which can be used for diagnostic purposes.
Most studies use the κ-FLC index to determine an intrathecal κ-FLC synthesis, he said. The calculation is as follows: 
Another possibility is the absolute CSF κ-FLC concentration, used in many studies and by many laboratories, he noted.