Kappa free light chain and neurofilament light independently predict early multiple sclerosis disease activity—a cohort studyResearch in context
Harald Hegen,
Klaus Berek,
Gabriel Bsteh,
Michael Auer,
Patrick Altmann,
Franziska Di Pauli,
Astrid Grams,
Dejan Milosavljevic,
Markus Ponleitner,
Paulina Poskaite,
Christine Schnabl,
Sebastian Wurth,
Anne Zinganell,
Thomas Berger,
Janette Walde,
Florian Deisenhammer
Affiliations
Harald Hegen
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria; Corresponding author. Department of Neurology, Medical University of Innsbruck, Anichstraße 35, A-6020, Innsbruck.
Klaus Berek
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Gabriel Bsteh
Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
Michael Auer
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Patrick Altmann
Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
Franziska Di Pauli
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Astrid Grams
Department of Neuroradiology, Medical University of Innsbruck, Innsbruck, Austria
Dejan Milosavljevic
FH Campus Wien, University of Applied Sciences, Vienna, Austria
Markus Ponleitner
Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
Paulina Poskaite
Department of Neuroradiology, Medical University of Innsbruck, Innsbruck, Austria
Christine Schnabl
FH Campus Wien, University of Applied Sciences, Vienna, Austria
Sebastian Wurth
Department of Neurology, Medical University of Graz, Graz, Austria
Anne Zinganell
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Thomas Berger
Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
Janette Walde
Department of Statistics, Faculty of Economics and Statistics, University of Innsbruck, Innsbruck, Austria; Corresponding author. Department of Statistics, Faculty of Economics and Statistics, University of Innsbruck, Universitätsstraße 15, A-6020, Innsbruck.
Florian Deisenhammer
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Summary: 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.
