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Published on: November 29, 2019
High levels of cerebrospinal fluid free kappa chains predict conversion to multiple sclerosis
Luisa M Villar1, Mercedes Espiño, Lucienne Costa-Frossard
1Multiple Sclerosis Unit, Department of Immunology, Ramón y Cajal University Hospital, Madrid, Spain.
Insights
High levels of free kappa chains (FKC) in cerebrospinal fluid (CSF) accurately predict conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS). This biomarker aids in identifying high-risk patients for early intervention.
Area of Science:
- Neurology
- Biomarker Discovery
Background:
- Clinically isolated syndrome (CIS) can be an early sign of multiple sclerosis (MS), but not all patients convert.
- Identifying CIS patients at high risk for MS conversion is crucial for timely treatment and improved outcomes.
- Elevated free kappa chains (FKC) in cerebrospinal fluid (CSF) are observed in MS patients.
Purpose of the Study:
- To evaluate the accuracy of a new nephelometric test for measuring CSF FKC levels.
- To determine if CSF FKC levels can predict the conversion of CIS patients to clinically definite MS.
Main Methods:
- Assessed the linearity and inter-assay variability of the FKC test for CSF.
- Quantified CSF FKC levels in 25 non-inflammatory neurological disease (NIND) patients and 78 CIS patients.
- Analyzed the association between high CSF FKC levels and conversion to MS using Cox regression.
Main Results:
- The FKC test demonstrated good linearity (0.98) and inter-assay correlation (0.99).
- A cut-off value of 0.53 mg/l was established for CSF FKC.
- CIS patients with CSF FKC above the cut-off showed significantly earlier conversion to MS (HR=6.41, p=0.003).
Conclusions:
- Elevated CSF FKC levels are a reliable predictor of MS conversion in CIS patients.
- This finding supports the use of CSF FKC measurement as a diagnostic tool in neurology.
Background:
A clinically isolated syndrome (CIS) may be the initial presentation of multiple sclerosis (MS). However, some CIS never develop MS. The identification of patients at risk of MS conversion is crucial as early treatment may improve their outcome. Free kappa chains (FKC) are increased in cerebrospinal fluid (CSF) of MS patients. We studied the accuracy of CSF FKC level measurement, using a new nephelometric test, to predict conversion of CIS patients to MS.
Methods:
We calculated linearity and inter-assay variability of the FKC test for CSF values and quantified this protein in CSF from 25 patients with non-inflammatory neurological diseases (NIND) and 78 consecutive CIS patients. We assessed whether high CSF FKC levels associate with CIS conversion to clinically definite MS, defined as the onset of new relapses during follow-up.
Results:
Between 0.1 and 5mg/l the FKC test showed linearity of 0.98 and inter-assay correlation coefficient of =0.99. A cut-off value of 0.53 mg/l (mean+2SD of NIND group CSF FKC values) was calculated. CIS patients with CSF FKC above this value showed earlier conversion to MS in univariate and multivariate Cox analysis (HR=6.41; 95% CI=1.88-21.78, p=0.003).
Conclusion:
High CSF FKC levels accurately predict CIS patient conversion to MS.
Related Concept Videos
Multiple Sclerosis l: Introduction
Cerebral Edema ll: Pathophysiology

