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Optimizing kappa free light chain index thresholds for multiple sclerosis (MS) diagnosis in low-MS prevalence
Su-Hyun Kim1, You-Ri Kang2, Jieun Chung1
1Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
Insights
The kappa free light chain (KFLC) index effectively diagnoses multiple sclerosis (MS) in Asian populations. Optimized, sex-specific thresholds enhance diagnostic accuracy for MS, especially where conditions like NMOSD and MOGAD are common.
Area of Science:
- Neurology
- Immunology
- Biomarker Discovery
Background:
- The kappa free light chain (KFLC) index is a validated marker for intrathecal immunoglobulin synthesis.
- Its diagnostic utility for multiple sclerosis (MS) in Asian populations, where MS mimics are prevalent, is not well-established.
Purpose of the Study:
- To validate the KFLC index for diagnosing MS in a Korean cohort.
- To determine optimal KFLC index thresholds for MS diagnosis in this population.
Main Methods:
- Retrospective analysis of 208 patients with cerebrospinal fluid (CSF) evaluation.
- Comparison of KFLC index and other biomarkers between MS and non-MS groups (including NMOSD, MOGAD).
- Receiver operating characteristic (ROC) analysis to identify diagnostic thresholds.
Main Results:
- An optimal KFLC index threshold of ⩾12.6 demonstrated 84% sensitivity and 74% specificity for MS diagnosis.
- Combining the KFLC index with oligoclonal bands (OCBs) increased specificity to 93%.
- Sex-specific thresholds (⩾22.8 for females, ⩾7.0 for males) improved diagnostic performance.
Conclusions:
- The KFLC index is a reliable biomarker for MS diagnosis in Asian populations.
- Optimized and sex-specific thresholds enhance diagnostic precision, particularly in regions with high prevalence of MS mimics.
- Findings align with the global diagnostic performance of the KFLC index for MS.
Background:
The kappa free light chain (KFLC) index is a quantitative marker of intrathecal immunoglobulin synthesis with diagnostic performance comparable to cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCBs). Its utility in Asian populations, where multiple sclerosis (MS) is less prevalent and mimics such as neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD) are common, remains underexplored.
Objectives:
We aimed to validate the KFLC index and determine optimal thresholds for MS diagnosis in a Korean cohort.
Methods:
We retrospectively analyzed 208 patients undergoing CSF evaluation, including 103 with MS and 105 with non-MS conditions (64 NMOSD, 14 MOGAD, 27 others). KFLC-related biomarkers were compared, and receiver operating characteristic analyses identified thresholds.
Results:
When comparing the MS group (n = 103) with the non-MS group (n = 105), the optimal KFLC index threshold was ⩾12.6, yielding sensitivity 84%, specificity 74%, and accuracy 79%. Combining KFLC index ⩾12.6 with OCB positivity increased specificity to 93%. Sex-specific thresholds (⩾22.8 for females, ⩾7.0 for males) improved performance, increasing male sensitivity and female specificity reaching 82%.
Conclusion:
The KFLC index is a reliable biomarker for MS diagnosis in Asian populations. Optimized and sex-specific thresholds may enhance diagnostic precision where MS mimics are relatively prevalent, consistent with diagnostic performance globally.
