Kappa Free Light Chain Index Predicts Long-term Disease Activity and Disability Worsening in Multiple Sclerosis
Harald Hegen1, Klaus Berek1, Martin Schmidauer1, Gabriel Bsteh2, Michael Auer1, Robert Barket1, Thomas Berger2, Franziska Di Pauli1, Astrid Grams1, Michaela Hassler3, Lukas Lenhart1, Dejan Milosavljevic3, Anne Zinganell1, Janette Walde4, Florian Deisenhammer1
1Medical University of Innsbruck, 2Medical University of Vienna, 3University of Applied Sciences Vienna, 4University of Innsbruck
Objective:

To investigate whether κ-free light chain (FLC) index determined at disease onset predicts multiple sclerosis (MS) disease activity over a period of 10 years. 

Background:

κ-FLC index predicts short-term disease activity in early MS. The prognostic value of this biomarker over the long-term is largely unknown. 

Design/Methods:

Patients with a first demyelinating event of the central nervous system who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for 10 (±5) years. At baseline age, sex, disease duration as well as number of T2 hyperintense lesions (T2L) and contrast-enhancing lesions (CEL) on MRI were determined. During follow-up, the occurrence of relapse, Expanded Disability Status Scale (EDSS) scores and the initiation of disease-modifying treatment (DMT) were registered. κ-FLC were measured by nephelometry and κ-FLC index was calculated as (CSF κ-FLC/serum κ-FLC)/albumin quotient. 

Results:

A total of 64 patients with a median age of 32 years (25th-75th percentile: 27-39) and a female predominance of 75% were followed over median of 113 (90-129) months. Forty-six (72%) patients experienced relapse and 30 (47%) showed disability worsening during follow-up. Multivariable Cox regression analysis adjusted for age, sex, disease duration, number of T2L, CEL, and the administration of DMT, revealed that κ-FLC index predicts time to relapse (Hazard ratio (HR): 1.45, lower limit (LL) of 95%-confidence interval (CI): 1.002, per increase of 100, p=0.049) and disability worsening (HR: 1.86, LL-CI: 1.22, p=0.008). At year 10, the estimated chance to remain free of relapse was decreased by 40% in patients with high κ-FLC index (>100) compared to patients with low κ-FLC index (≤100), the probability to remain without disability worsening was 27% lower. 

Conclusions:

κ-FLC index predicts long-term MS disease activity and disability worsening independent of other risk factors. 

10.1212/WNL.0000000000210620
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