The Kappa Free Light Chains Index in Multiple Sclerosis: From Emerging Evidence to Clinical Application
Noé Verchere1, Ségolène Roult1, Laure Michel2
1Biochemistry Laboratory, CHU Pontchaillou, Rennes, France.
Journal of Neurochemistry
|April 1, 2026
Summary
The kappa free light chain (KFLC) index aids multiple sclerosis (MS) diagnosis by detecting intrathecal immunoglobulin synthesis. A new algorithm integrating KFLC-index and OCBs improves diagnostic accuracy for MS.
Area of Science:
- Neurology
- Immunology
- Biomarker Discovery
Background:
- The kappa free light chain (KFLC) index shows promise for detecting intrathecal immunoglobulin synthesis in multiple sclerosis (MS).
- Current clinical use is hampered by inconsistent thresholds and a lack of standardized diagnostic algorithms.
- Oligoclonal bands (OCBs) are established biomarkers, but quantitative, automated alternatives are needed.
Purpose of the Study:
- To develop and validate a diagnostic algorithm for MS that incorporates the KFLC-index with existing biomarkers like CSF-restricted OCBs.
- To establish standardized diagnostic criteria for MS utilizing the KFLC-index.
- To improve the accuracy and automation of MS diagnosis.
Main Methods:
- A prospective, monocentric study involved 198 patients with suspected neurological disease undergoing lumbar puncture.
- Paired cerebrospinal fluid (CSF) and serum KFLC and LFLC were quantified using a turbidimetric assay.
- A diagnostic algorithm was developed and validated in independent cohorts, with performance assessed by ROC analysis.
Main Results:
- The KFLC-index demonstrated excellent diagnostic accuracy (AUC=0.93) in the derivation cohort.
- An optimal threshold of 20.27 yielded 80.6% sensitivity and 100% specificity for MS diagnosis.
- The validated algorithm showed consistent performance, with OCBs aiding interpretation in intermediate KFLC-index ranges.
Conclusions:
- The KFLC-index is a reliable biomarker for MS diagnosis.
- Integrating the KFLC-index into a tiered diagnostic algorithm significantly enhances diagnostic performance.
- Local validation is crucial for widespread clinical adoption of the KFLC-index algorithm.
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