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Kappa free light chain index in CSF diagnostics: the impact of different immunoglobulin isotypes
Martin Schmidauer1, Klaus Berek1, Michael Auer1
1Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Insights
The kappa free light chain (κ-FLC) index in multiple sclerosis (MS) is mainly elevated by intrathecal IgG synthesis. Intrathecal IgM synthesis contributes less significantly to the κ-FLC index in MS patients.
Area of Science:
- Neurology
- Immunology
- Biochemistry
Background:
- The kappa free light chain (κ-FLC) index is a key marker for intrathecal immunoglobulin synthesis in cerebrospinal fluid (CSF).
- Its use is increasing in diagnosing multiple sclerosis (MS), but the specific contributions of different immunoglobulin (Ig) isotypes are not fully understood.
Purpose of the Study:
- To investigate the relative contributions of different immunoglobulin isotypes to intrathecal κ-FLC production.
- To clarify the role of IgG, IgM, and IgA in elevating the κ-FLC index in patients with suspected MS.
Main Methods:
- Retrospective analysis of CSF and serum data from 188 patients with a first demyelinating event suggestive of MS.
- Linear regression analysis was employed to determine the impact of intrathecal immunoglobulin fractions (IF) on the κ-FLC index.
Main Results:
- The κ-FLC index was significantly higher in patients with intrathecal IgG synthesis compared to those without.
- Both IgG and IgM IF independently contributed to the κ-FLC index, with IgG IF showing a substantially larger effect size (approx. 3.5 times).
- IgA IF also showed a similar qualitative contribution to the κ-FLC index.
Conclusions:
- Intrathecal IgG synthesis is the primary driver of elevated κ-FLC index in MS patients.
- Intrathecal IgM synthesis has a less frequent and quantitatively smaller impact on the κ-FLC index.
Background:
The kappa free light chain (κ-FLC) index is a sensitive marker of intrathecal immunoglobulin (Ig) synthesis and is increasingly used in cerebrospinal fluid (CSF) analysis of patients with suspected multiple sclerosis (MS). The relative contribution of the different Ig isotypes to intrathecal κ-FLC production remains unclear.
Methods:
We retrospectively analysed CSF data from patients with a first demyelinating event suggestive of MS enrolled in studies at the Medical Universities of Innsbruck and Vienna. Of all included patients, results on Ig and κ-FLC concentrations in CSF and serum were available. Linear regression analysis was used to assess the impact of Ig intrathecal fractions (IF) on κ-FLC index.
Results:
A total of 188 patients with a median age of 31 (25-39) years and a predominantly female sex distribution (62%) were included. The κ-FLC index was significantly higher in patients with isolated intrathecal IgG synthesis [32.5 (17.7-81.0); n=130] compared to patients without intrathecal immunoglobulin production [3.0 (2.0-5.9); p<0.001; n=18] and was further elevated in patients with both intrathecal IgG and IgM synthesis [68.4 (48.4-120.6); n=29]. Both IgG and IgM IF independently contributed to the κ-FLC index in linear regression analysis, with IgG IF having approximately 3.5 times the effect size of IgM IF. Exploratory analysis of the contribution of IgA IF to κ-FLC index revealed qualitatively the same results.
Conclusion:
Increase of κ-FLC index in patients with MS is predominantly due to an intrathecal IgG synthesis, while the contribution of intrathecal IgM is less frequent and quantitatively low.
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