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Updated: Apr 4, 2026
Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
Published on: November 29, 2019
Kappa free light chains in cerebrospinal fluid to detect inflammation - results from a multicentric prospective
Marie Süße1, Malte Johannes Hannich2,3, Felix Lottermoser1
1Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
Insights
Free light chains kappa (FLCκ) show promise for detecting intrathecal immunoglobulin synthesis. However, this study found FLCκ did not meet the high sensitivity threshold for standalone use in routine diagnostics.
Area of Science:
- Neurology
- Immunology
- Laboratory Diagnostics
Background:
- Free light chains kappa (FLCκ) are emerging biomarkers for detecting intrathecal immunoglobulin synthesis.
- A nationwide study (ORCAS) evaluated FLCκ integration into routine cerebrospinal fluid (CSF) diagnostics.
Purpose of the Study:
- To assess if FLCκ testing in CSF can reliably predict intrathecal immunoglobulin (Ig) synthesis.
- To determine the sensitivity and negative predictive value (NPV) of FLCκ for detecting Ig synthesis and CSF-specific oligoclonal bands (OCB).
Main Methods:
- Prospective, multicenter study involving 1052 paired CSF and serum samples from six German laboratories.
- Measurement of FLCκ levels in CSF and serum according to local laboratory standards.
Main Results:
- The intrathecal fraction of FLCκ predicted intrathecal Ig synthesis with 87% sensitivity and 97% NPV.
- FLCκ sensitivity for predicting CSF-specific OCB was 93%.
Conclusions:
- The study did not achieve the primary endpoint of >0.95 sensitivity for FLCκ in detecting intrathecal Ig synthesis.
- FLCκ is not recommended as a standalone preselection marker but may offer added value when used with existing diagnostic parameters.
Background:
Free light chain kappa (FLCκ) have emerged as a sensitive biomarker to detect intrathecal immunoglobulin synthesis. To evaluate the role of FLCκ in routine cerebrospinal fluid laboratory diagnostics we conducted a prospective nationwide real world diagnostic study for evaluating the integration of kappa free light chain into clinical routine (ORCAS - prospective multicenter validation of a new laboratory workflow integrating the free light chains kappa in CSF analysis).
Objectives:
To determine whether testing for intrathecal synthesis of FLCκ in cerebrospinal fluid (CSF) can predict intrathecal immunoglobulin (Ig) synthesis of total IgG, IgA, IgM or CSF-specific oligoclonal bands (OCB) with high sensitivity.
Materials & Methods:
FLCκ were measured in 1052 paired CSF and serum samples according to local laboratory standards in six laboratories in Germany. Sensitivity and negative predictive value (NPV) of intrathecal FLCκ synthesis as first line detection of intrathecal Ig synthesis were assessed.
Results:
Of the 1052 samples, 624 fulfilled the inclusion criteria. The intrathecal fraction of FLCκ predicted intrathecal Ig synthesis with a sensitivity of 0.87 (CI 0.81-0.93) and a NPV of 0.97 (CI 0.95-0.98). The sensitivity for predicting CSF-specific OCB was 0.93 (CI 0.88-0.98).
Conclusions:
In the real world setting this study analyzing FLCk for detecting intrathecal Ig synthesis did not reach its prespecified primary endpoint of sensitivity >0.95. Therefore, FLCκ should not yet be introduced as a stand-alone preselection marker for intrathecal Ig synthesis, but may provide additional value when combined with established diagnostic parameters.
