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Prognostic value of kappa free light chain index in patients with primary progressive multiple sclerosis
Martin Schmidauer1, Klaus Berek1, Michael Auer1
1Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Background:
The kappa free light chain (κ-FLC) index is a well-established biomarker in multiple sclerosis (MS). While the prognostic value of the κ-FLC index has been demonstrated in early relapsing-remitting MS, its prognostic value in primary progressive MS (PPMS) has not yet been investigated.
Methods:
In this multicenter, retrospective cohort study, patients diagnosed with PPMS with diagnostic lumbar puncture and clinical follow-up of at least 12 months were recruited from nine MS centers across five countries. At baseline, age, sex, disease duration, and the number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CEL) on MRI were determined. κ-FLC was measured using nephelometry/turbidimetry, and the κ-FLC index was calculated as (CSF κ-FLC/serum κ-FLC)/albumin quotient. At follow-up, the occurrence of disability progression and the administration of disease-modifying treatment (DMT) were registered. The primary endpoint was time to disability progression.
Results:
A total of 121 PPMS patients were included with a median age of 53 years (25th-75th percentile: 46-59) and a balanced sex distribution (48.8% female). Multivariable Cox regression analysis revealed no significant association between the κ-FLC index and disability progression [hazard ratio (HR) 1.0, p = 0.950]. Prior use of DMT (HR 0.60, p = 0.023) and brain T2L > 9 at baseline (HR 2.22, p = 0.026) were significantly associated with disability progression. The remaining covariates, including age, sex, disease duration, and CEL, showed no significant associations.
Conclusion:
The κ-FLC index does not predict disability progression in PPMS, contrasting its growing role as a prognostic biomarker in relapsing MS. This highlights phenotypic differences in MS pathophysiology and underscores the need for prognostic biomarkers in PPMS.
Insights
The kappa free light chain (κ-FLC) index does not predict disability progression in primary progressive multiple sclerosis (PPMS). This finding highlights differences between PPMS and relapsing MS, emphasizing the need for new PPMS biomarkers.
Area of Science:
- Neurology
- Immunology
- Biomarker Research
Background:
- The kappa free light chain (κ-FLC) index is an established prognostic biomarker in relapsing-remitting multiple sclerosis (MS).
- Its prognostic utility in primary progressive multiple sclerosis (PPMS) remains uninvestigated.
- Understanding prognostic markers is crucial for managing MS subtypes.
Purpose of the Study:
- To investigate the prognostic value of the κ-FLC index in predicting disability progression in patients with PPMS.
- To compare the prognostic role of the κ-FLC index in PPMS with its known role in relapsing MS.
Main Methods:
- A multicenter, retrospective cohort study involving 121 PPMS patients from nine MS centers.
- Baseline assessment included demographics, disease duration, MRI lesion load (T2L, CEL), and κ-FLC index measurement.
- Clinical follow-up assessed time to disability progression and disease-modifying treatment (DMT) administration.
Main Results:
- The κ-FLC index was not significantly associated with disability progression in PPMS (HR 1.0, p = 0.950).
- Prior DMT use (HR 0.60, p = 0.023) and a higher baseline T2 lesion load (T2L > 9; HR 2.22, p = 0.026) were significantly associated with disability progression.
- Age, sex, disease duration, and contrast-enhancing lesions (CEL) did not show significant associations.
Conclusions:
- The κ-FLC index does not serve as a predictor of disability progression in PPMS.
- This suggests distinct pathophysiological mechanisms between PPMS and relapsing MS.
- There is a critical need for the development of specific prognostic biomarkers for PPMS.
