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Kappa free light chain and neurofilament light independently predict early multiple sclerosis disease activity-a
Harald Hegen1, Klaus Berek1, Gabriel Bsteh2
1Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Background:
Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity.
Methods:
Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated.
Findings:
A total of 86 patients at a mean age of 33 ± 10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3).
Interpretation:
κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors.
Funding:
This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society.
Insights
Serum neurofilament light (sNfL) and kappa-free light chain (κ-FLC) index predict multiple sclerosis (MS) activity. These markers offer additive value for forecasting early MS disease progression.
Area of Science:
- Neurology
- Biomarker Discovery
- Immunology
Background:
- Multiple sclerosis (MS) exhibits highly variable disease courses.
- Predicting MS progression is crucial for timely intervention.
- Current predictors do not fully capture disease heterogeneity.
Purpose of the Study:
- To evaluate the additive predictive value of kappa-free light chain (κ-FLC) index and serum neurofilament light (sNfL) for MS disease activity.
- To determine if these biomarkers improve prediction beyond established factors.
Main Methods:
- Longitudinal study of early MS patients with baseline cerebrospinal fluid and serum samples.
- Measurement of κ-FLC index and sNfL Z scores.
- Follow-up for four years to assess clinical attacks and treatment initiation.
Main Results:
- Both κ-FLC index and sNfL Z score independently predicted time to a second clinical attack.
- A combination of high κ-FLC index and high sNfL Z score indicated the lowest chance of remaining relapse-free.
- Lower levels of both markers were associated with a higher chance of remaining relapse-free.
Conclusions:
- κ-FLC index and sNfL Z score possess additive predictive value for early MS disease activity.
- These biomarkers offer independent prediction beyond known MS predictors.
- This finding aids in personalized risk stratification for MS patients.
