Kappa free light chain index as a diagnostic and prognostic biomarker in multiple sclerosis
Luis Moreno-Navarro1,2, Sergio Mora-Diaz3, Lourdes Ruiz-Escribano-Menchen4,5
1Neurology Department, Dr. Balmis General University Hospital, C/Pintor Baeza 12, 03010, Alicante, Spain. moreno_luinav@gva.es.
Background:
The proposed 2024 McDonald criteria incorporate the kappa free light chain (KFLC) index as an additional biomarker in multiple sclerosis (MS) diagnosis. Emerging evidence suggests that a high KFLC index may relate to worse outcomes in people with MS (pwMS). This study had two main objectives: to evaluate the diagnostic performance of the KFLC index against the 2017 and proposed 2024 clinico-radiological McDonald criteria, and to explore its prognostic significance.
Methods:
We performed a retrospective cohort study of adults with a first episode suggestive of MS (2019-2024). All underwent lumbar puncture with simultaneous determination of the KFLC index and oligoclonal bands (OCB).
Results:
Among 150 participants, OCB showed sensitivities of 85.9% (2017) and 86.6% (2024) with specificities of 79.7% and 81.9%. A KFLC index cut-off of 12.0 yielded sensitivities of 87.5% (2017) and 88.1% (2024) with specificities of 79.2% and 81.4%, comparable to OCB. In pwMS, KFLC index ≥ 100 was associated with younger age (OR 1.53, p = 0.048), women (OR 1.53, p = 0.037), relapses (OR 2.30, p = 0.029) and new infratentorial or spinal cord (SC) lesions (OR 6.90, p = 0.003). In multivariable analysis, KFLC index ≥ 100 remained associated with new infratentorial or SC lesions (aOR 8.07, p = 0.019).
Conclusion:
The KFLC index shows diagnostic utility comparable to OCB; however, it is an adjunctive biomarker that complements clinical and MRI findings and should not be used as a standalone diagnostic test. An elevated KFLC index was associated with short-term accrual of infratentorial or SC lesions; these exploratory findings require validation in larger, longer-term cohorts.
Insights
The kappa free light chain (KFLC) index shows diagnostic performance comparable to oligoclonal bands (OCB) for multiple sclerosis (MS). An elevated KFLC index may indicate a higher risk of new lesions in the brainstem or spinal cord in people with MS.
Area of Science:
- Neurology
- Biomarker Discovery
- Diagnostic Criteria
Background:
- The 2024 McDonald criteria propose incorporating the kappa free light chain (KFLC) index for multiple sclerosis (MS) diagnosis.
- Emerging research suggests a high KFLC index may correlate with poorer outcomes in people with MS (pwMS).
- This study investigates the diagnostic and prognostic roles of the KFLC index in MS.
Purpose of the Study:
- To assess the diagnostic accuracy of the KFLC index compared to the 2017 and proposed 2024 McDonald criteria.
- To explore the prognostic value of the KFLC index in pwMS.
- To evaluate the KFLC index's utility alongside oligoclonal bands (OCB) in MS diagnosis.
Main Methods:
- Retrospective cohort study of 150 adults with a first episode suggestive of MS (2019-2024).
- Simultaneous determination of KFLC index and OCB via lumbar puncture.
- Comparison of diagnostic performance against established and proposed McDonald criteria.
Main Results:
- KFLC index diagnostic performance (sensitivity 87.5%, specificity 79.2% at cut-off 12.0) was comparable to OCB.
- An elevated KFLC index (≥100) was associated with younger age, female sex, relapses, and new infratentorial or spinal cord lesions.
- In multivariable analysis, KFLC index ≥100 remained significantly associated with new infratentorial or spinal cord lesions (aOR 8.07, p=0.019).
Conclusions:
- The KFLC index demonstrates diagnostic utility comparable to OCB, serving as an adjunctive biomarker for MS.
- It should complement, not replace, clinical and MRI findings in MS diagnosis.
- Elevated KFLC index is linked to short-term accrual of infratentorial or spinal cord lesions, warranting further validation.
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